# NM_001083961.2(WDR62):c.3711_3714del (p.Ser1237fs)

https://sugi.bio/variant/wdr62-p-ser1237fs

## Summary

**WDR62 p.Ser1237fs (c.3711_3714del)** is classified **Likely pathogenic** in WDR62 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). No gnomAD frequency available for this variant; Associated with microcephaly 2, primary, autosomal recessive, with or without cortical malformations.

**At a glance:** Likely pathogenic · review: Single submitter · rsID rs2513785351 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the WDR62 gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to microcephaly 2, primary, autosomal recessive, with or without cortical malformations.

*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.*

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0015366/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [WDR62](https://sugi.bio/atlas/gene/WDR62/) |
| Protein change (HGVS p.) | p.Ser1237fs |
| Coding change (HGVS c.) | c.3711_3714del |
| MANE Select transcript | [NM_001083961](https://www.ncbi.nlm.nih.gov/nuccore/NM_001083961) |
| dbSNP | [rs2513785351](https://www.ncbi.nlm.nih.gov/snp/rs2513785351/) |
| Variant type | Deletion |
| Location | chr19:36103537-36103540 (GRCh38) |
| ClinVar | [VCV2690780](https://www.ncbi.nlm.nih.gov/clinvar/variation/2690780/) |

**All HGVS expressions:** `NC_000019.10:g.36103539_36103542del`, `NC_000019.9:g.36594441_36594444del`, `NG_028101.2:g.53644_53647del`, `NM_001083961.2:c.3711_3714del`, `NM_001411145.1:c.3696_3699del`, `NM_001411146.1:c.3462_3465del`, `NM_001411147.1:c.3360_3363del`, `NM_173636.5:c.3696_3699del`

## 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 0.779, GERP -0.483, phastCons 0.435 — weakly conserved position
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.806, pLI 1.0718e-25. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 30 of 32**, so the transcript is predicted to undergo NMD.
- 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.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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}

**WDR62** population constraint: LOEUF 0.806, pLI 1.0718e-25, missense-Z 1.767; ClinGen dosage — haploinsufficiency gene assoc. with recessive phenotype, triplosensitivity Not yet evaluated/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):

- **microcephaly 2, primary, autosomal recessive, with or without cortical malformations** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 61.19, 35% of residues very-high.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-11-06.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Revvity Omics, Revvity | Likely pathogenic | criteria provided, single submitter | clinical testing | 2023-11-06 |

## Associated conditions {#conditions}

[microcephaly 2, primary, autosomal recessive, with or without cortical malformations](https://sugi.bio/atlas/disease/microcephaly-2-primary-autosomal-recessive-with-or-without-cortical-malformations/).

**Reported phenotype names (ClinVar):** Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MICROCEPHALY 2, PRIMARY, AUTOSOMAL RECESSIVE, WITH CORTICAL MALFORMATIONS, WDR62 Primary Microcephaly.

## Similar variants {#similar}

Related WDR62 variant pages (same residue, condition, or type): [WDR62 p.Ser696fs](/variant/wdr62-p-ser696fs), [WDR62 p.Thr1244fs](/variant/wdr62-p-thr1244fs), [WDR62 c.1233+1del](/variant/wdr62-c-1233-plus-1del), [WDR62 c.270-15_287del](/variant/wdr62-c-270-minus-15-287del), [WDR62 c.2740_2743del](/variant/wdr62-c-2740-2743del), [WDR62 p.Ala1157fs](/variant/wdr62-p-ala1157fs), [WDR62 p.Ala865fs](/variant/wdr62-p-ala865fs), [WDR62 p.Cys300fs](/variant/wdr62-p-cys300fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 2690780). 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.*