USH2A p.Cys1004=
c.3012T>C · rs745861155 · VCV2140802
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.4 | GERP -0.093, phastCons 1 |
| Overall | ||
| CADD | 9.952 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.00774%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00579%
Overall
0.00205%
33/1,613,128 alleles · ultra-rare
exomes 27/1,460,846 · genomes 6/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| Admixed American | 0.015% | 6,661 |
| European (non-Finnish) | 0.00187% | 53,606 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,468 |
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.Cys1004=
- Coding
- c.3012T>C
- MANE Select
- NM_206933
- dbSNP
- rs745861155
- Type
- single nucleotide variant
- Location
- chr1:216217532 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1004
- the laminin egf-like 10 domain; a disulfide bond
Similar variants
- USH2A p.Cys1004Phe Uncertain significance ★ ⚠ same residue
- USH2A c.12295-3T>A Pathogenic ★★★ same type
- USH2A c.8559-2A>G Pathogenic ★★★ same type
- USH2A c.8682-9A>G Pathogenic ★★★ same type
- USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same type
- USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same type
- USH2A p.Arg4192Cys Likely pathogenic ★★★ ⚠ same type
- USH2A p.Asn346His Pathogenic ★★★ same type
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-cys1004 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown