USH2A p.Asp642=
c.1926C>T · rs1159551018 · VCV1130977
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1 | GERP -3.6 |
| Overall | ||
| CADD | 0.205 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,926 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000372%
6/1,613,860 alleles · very rare
exomes 4/1,461,690 · genomes 2/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,732 |
| Admixed American | 0.00333% | 30,002 |
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.Asp642=
- Coding
- c.1926C>T
- MANE Select
- NM_206933
- dbSNP
- rs1159551018
- Type
- single nucleotide variant
- Location
- chr1:216289325 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 642
- the laminin egf-like 3 domain
Similar variants
- USH2A p.Asp642His 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-asp642 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown