USH1C p.Phe108=
c.324T>C · rs549758189 · VCV763194
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.718%, sas)
Conditions
1
Usher syndrome type 1C
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 -1.4 | GERP -5.3 |
| Overall | ||
| CADD | 5.585 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.718%
South Asian · 654/91,070 alleles
Filtering AF
0.672%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.654%
Overall
0.0416%
672/1,614,114 alleles · rare
exomes 645/1,461,842 · genomes 27/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.718% | 139 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| European (non-Finnish) | 8.47e-05% | 1,180,030 |
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
- USH1C
- Protein
- p.Phe108=
- Coding
- c.324T>C
- MANE Select
- NM_153676
- dbSNP
- rs549758189
- Type
- single nucleotide variant
- Location
- chr11:17531217 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 79.51 · 11 PDB
- Residue 108
- the pdz 1 domain; an α-helix
Similar variants
- USH1C c.1020-2A>C Likely pathogenic ★★ same condition
- USH1C c.104+1G>A Pathogenic/Likely pathogenic ★★ same condition
- USH1C c.104+5G>C Likely pathogenic ★★ same condition
- USH1C c.2227-1G>T Pathogenic/Likely pathogenic ★★ same condition
- USH1C c.2280+2T>C Likely pathogenic ★★ same condition
- USH1C c.248+1G>A Likely pathogenic ★★ same condition
- USH1C c.249-1G>A Likely pathogenic ★★ same condition
- USH1C c.2490+1G>A Likely 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/ush1c-p-phe108 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown