# NM_000275.3(OCA2):c.2430del (p.Phe810fs)

https://sugi.bio/variant/oca2-p-phe810fs

## Summary

**OCA2 p.Phe810fs (c.2430del)** is classified **Uncertain significance** in OCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Associated with oculocutaneous albinism type 2.

**At a glance:** Uncertain significance · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the OCA2 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter, and is linked to oculocutaneous albinism type 2.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Infancy, Neonatal |
| Prevalence | 6-9 / 10 000 (Specific population) |
| Diagnostic panels | OCA2 is a diagnostic-grade gene on 4 Genomics England panels |

**Commonly reported features of Oculocutaneous albinism type 2** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Abnormality of refraction — Frequent (79-30%)
- Photophobia — Frequent (79-30%)
- Blue irides — Frequent (79-30%)
- Nystagmus — Frequent (79-30%)
- Hypopigmentation of the skin — Frequent (79-30%)
- Heterochromia iridis — Frequent (79-30%)
- Freckling — Frequent (79-30%)
- White eyebrow — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0004038/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [OCA2](https://sugi.bio/atlas/gene/OCA2/) |
| Protein change (HGVS p.) | p.Phe810fs |
| Coding change (HGVS c.) | c.2430del |
| MANE Select transcript | [NM_000275](https://www.ncbi.nlm.nih.gov/nuccore/NM_000275) |
| Variant type | Deletion |
| Location | chr15:27844961-27844961 (GRCh38) |
| ClinVar | [VCV3776100](https://www.ncbi.nlm.nih.gov/clinvar/variation/3776100/) |

**All HGVS expressions:** `NC_000015.10:g.27844961del`, `NC_000015.9:g.28090107del`, `NG_009846.1:g.259352del`, `NG_009846.2:g.259354del`, `NM_000275.3:c.2430del`, `NM_001300984.2:c.2358del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 7.683, GERP 1.61, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.869, pLI 1.9006e-14. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **within the last 50 nt of the penultimate exon (23 of 24, 2 nt from its 3' end)** — predicted to **escape NMD**, so the truncated protein is likely expressed. An input to PVS1, not an applied code.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**OCA2** population constraint: LOEUF 0.869, pLI 1.9006e-14, missense-Z 0.96565; ClinGen dosage — haploinsufficiency gene assoc. with recessive phenotype, triplosensitivity 0/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **oculocutaneous albinism type 2** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 73.79, 27% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of OCA2 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** OCA2's established molecular role includes chloride channel activity.


### Pathways affected {#pathways}

OCA2 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Melanin biosynthesis](https://reactome.org/content/detail/R-HSA-5662702) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** chloride channel activity.

**Biological process:** melanin biosynthetic process from tyrosine, lysosomal lumen pH elevation.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-07-17.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| 3billion | Uncertain significance | criteria provided, single submitter | clinical testing | 2023-07-17 |

## Associated conditions {#conditions}

[oculocutaneous albinism type 2](https://sugi.bio/atlas/disease/oculocutaneous-albinism-type-2/).

**Reported phenotype names (ClinVar):** Tyrosinase-positive oculocutaneous albinism, ALBINISM II, Oculocutaneous albinism type 2, Albinism, oculocutaneous, type II.

## Similar variants {#similar}

Related OCA2 variant pages (same residue, condition, or type): [OCA2 p.Ala696fs](/variant/oca2-p-ala696fs), [OCA2 p.Arg137fs](/variant/oca2-p-arg137fs), [OCA2 p.Arg53fs](/variant/oca2-p-arg53fs), [OCA2 p.Asn603fs](/variant/oca2-p-asn603fs), [OCA2 p.Glu253fs](/variant/oca2-p-glu253fs), [OCA2 p.Gly44fs](/variant/oca2-p-gly44fs), [OCA2 p.Leu207_Leu212del](/variant/oca2-p-leu207-leu212del), [OCA2 p.Leu316_Leu317insTer](/variant/oca2-p-leu316-leu317inster).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3776100). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*