USH2A p.Pro3613=
c.10839T>C · rs1002437761 · VCV3028675
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
Conditions
1
inherited retinal dystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -3.9 |
| Overall | ||
| CADD | 0.205 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,870 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00031%
5/1,614,014 alleles · ultra-rare
exomes 5/1,461,878 · genomes 0/152,136 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- USH2A
- Protein
- p.Pro3613=
- Coding
- c.10839T>C
- MANE Select
- NM_206933
- dbSNP
- rs1002437761
- Type
- single nucleotide variant
- Location
- chr1:215779943 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3613
- the fibronectin type-iii 21 domain
Similar variants
- USH2A c.8559-2A>G Pathogenic ★★★ same condition
- USH2A c.8682-9A>G Pathogenic ★★★ same condition
- USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same condition
- USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same condition
- USH2A p.Arg4192Cys Likely pathogenic ★★★ ⚠ same condition
- USH2A p.Asn346His Pathogenic ★★★ same condition
- USH2A p.Asn4292Asp Likely pathogenic ★★★ ⚠ same condition
- USH2A p.Cys759Phe Pathogenic ★★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ush2a-p-pro3613 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown