USH2A p.Ser3578=
c.10734T>C · rs1661658126 · VCV864738
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
Usher syndrome type 2A
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 1.2 | GERP -2.6, phastCons 0.46 |
| Overall | ||
| CADD | 1.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/75,032 alleles
Filtering AF
0.000442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,613,910 alleles · very rare
exomes 3/1,461,630 · genomes 0/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,516 |
| European (non-Finnish) | 8.48e-05% | 1,179,834 |
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.Ser3578=
- Coding
- c.10734T>C
- MANE Select
- NM_206933
- dbSNP
- rs1661658126
- Type
- single nucleotide variant
- Location
- chr1:215782048 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3578
- the fibronectin type-iii 20 domain
Similar variants
- USH2A p.Ser3578Asn Likely pathogenic ⚠ same residue
- USH2A c.12295-3T>A Pathogenic ★★★ same condition
- 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
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-ser3578 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown