# NM_001077620.3(PRCD):c.64C>T (p.Arg22Ter)

https://sugi.bio/variant/prcd-p-arg22ter

## Summary

**PRCD p.Arg22Ter (c.64C>T)** is classified **Pathogenic** in PRCD (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-08-04). Very rare (popmax 0.00162%, nfe); Associated with PRCD-related disorders.

**At a glance:** Pathogenic · review: Multiple submitters · rsID rs387907268 · 10 submitters · 4 linked conditions · very rare (popmax 0.00162%, nfe)

## For patients & families {#patients}

This is a change in the PRCD gene that is considered disease-causing, submitted by 10 submitters, and is linked to PRCD-related disorders.

*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:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [PRCD](https://sugi.bio/atlas/gene/PRCD/) |
| Protein change (HGVS p.) | p.Arg22Ter |
| Coding change (HGVS c.) | c.64C>T |
| MANE Select transcript | [NM_134268](https://www.ncbi.nlm.nih.gov/nuccore/NM_134268) (variant reported on NM_001077620) |
| dbSNP | [rs387907268](https://www.ncbi.nlm.nih.gov/snp/rs387907268/) |
| Variant type | single nucleotide variant |
| Location | chr17:76540205-76540205 (GRCh38) |
| ClinVar | [VCV37041](https://www.ncbi.nlm.nih.gov/clinvar/variation/37041/) |

**All HGVS expressions:** `NC_000017.10:g.74536287C>T`, `NC_000017.11:g.76540205C>T`, `NG_016702.1:g.17620C>T`, `NM_001077620.3:c.64C>T`

## 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 1.368, GERP 1.6, phastCons 0.999 — weakly conserved position
- Molecular consequence: **nonsense (stop-gain)** — a predicted loss-of-function variant. For a truncating variant the loss-of-function impact is position-dependent — C-terminal / last-exon truncations may escape nonsense-mediated decay. *Descriptive; not an applied PVS1 code.*
- CADD: **PHRED 36.0**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.00162%** (nfe) · FAF95 0.00104% · FAF99 0.000835% · 19/1,172,162 in the highest group · 21/1,587,346 alleles overall — very rare (popmax 0.00162%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| European (non-Finnish) (grpmax) | 0.00162% | 61,693 |
| Remaining individuals (not grpmax-eligible) | 0.00162% | 61,694 |
| South Asian | 0.00112% | 88,970 |

*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.*

## Clinical significance {#significance}

**Pathogenic** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2025-08-04.

**Submitter consensus:** unanimous (10/10 Pathogenic).

**Submission history:** 10 submissions (2010–2025); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| OMIM | Pathogenic | no assertion criteria provided | literature only | 2010-08-01 |
| Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Pathogenic | criteria provided, single submitter | clinical testing | 2023-01-01 |
| Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Pathogenic | criteria provided, single submitter | clinical testing | 2020-10-23 |
| 3billion | Pathogenic | criteria provided, single submitter | clinical testing | 2023-06-12 |
| First Genomix Gene Laboratory, Genetic Diagnostics Department | Pathogenic | criteria provided, single submitter | clinical testing | 2025-08-04 |
| Blueprint Genetics | Pathogenic | criteria provided, single submitter | clinical testing | 2024-07-16 |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | Pathogenic | no assertion criteria provided | clinical testing | 2016-09-01 |
| Sharon lab, Hadassah-Hebrew University Medical Center | Pathogenic | no assertion criteria provided | research | 2019-06-23 |
| Dept Of Ophthalmology, Nagoya University | Pathogenic | criteria provided, single submitter | research | 2023-10-01 |
| Labcorp Genetics (formerly Invitae), Labcorp | Pathogenic | criteria provided, single submitter | clinical testing | 2023-10-14 |

## Associated conditions {#conditions}

[PRCD-related disorders](https://sugi.bio/atlas/disease/prcd-related-disorders/), [retinitis pigmentosa 36](https://sugi.bio/atlas/disease/retinitis-pigmentosa-36/), [inherited retinal dystrophy](https://sugi.bio/atlas/disease/inherited-retinal-dystrophy/), [retinitis pigmentosa](https://sugi.bio/atlas/disease/retinitis-pigmentosa/).

**Reported phenotype names (ClinVar):** PRCD-related disorders, Retinitis pigmentosa 36, Retinitis pigmentosa, Retinal dystrophy, not provided, Inherited retinal dystrophy, none provided.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 37041). 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.*