USH2A p.Ala4207=
c.12621C>T · rs369544099 · VCV1105003
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, 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 -8.6 | GERP -3.5 |
| Overall | ||
| CADD | 0.094 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00477%
77/1,613,848 alleles · ultra-rare
exomes 56/1,461,804 · genomes 21/152,044 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,028 |
| African / African-American | 0.0254% | 3,940 |
| South Asian | 0.0154% | 6,505 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| East Asian | 0.00446% | 22,442 |
| Finnishnot grpmax-eligible | 0.00313% | 31,971 |
| European (non-Finnish) | 0.00271% | 36,875 |
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.Ala4207=
- Coding
- c.12621C>T
- MANE Select
- NM_206933
- dbSNP
- rs369544099
- Type
- single nucleotide variant
- Location
- chr1:215675290 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 4207
- the fibronectin type-iii 27 domain
Similar variants
- USH2A p.Ala4207Thr 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-ala4207 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown