USH1C p.Pro668=
c.2004C>A · rs201586291 · VCV667178
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.231%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.28 | GERP -5.8, phastCons 0.001 |
| Overall | ||
| CADD | 0.754 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.231%
Admixed American · 134/58,006 alleles
Filtering AF
0.199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.187%
Overall
0.00874%
138/1,578,306 alleles · rare
exomes 126/1,426,040 · genomes 12/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.231% | 433 |
| Remaining individualsnot grpmax-eligible | 0.00656% | 15,233 |
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.Pro668=
- Coding
- c.2004C>A
- MANE Select
- NM_153676
- dbSNP
- rs201586291
- Type
- single nucleotide variant
- Location
- chr11:17509365 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 79.51 · 11 PDB
Similar variants
- USH1C c.1020-2A>C Likely pathogenic ★★ same type
- USH1C c.104+1G>A Pathogenic/Likely pathogenic ★★ same type
- USH1C c.104+5G>C Likely pathogenic ★★ same type
- USH1C c.105-2A>G Pathogenic/Likely pathogenic ★★ same type
- USH1C c.2185-1G>A Likely pathogenic ★★ same type
- USH1C c.2226+2T>C Likely pathogenic ★★ same type
- USH1C c.2227-1G>T Pathogenic/Likely pathogenic ★★ same type
- USH1C c.2280+2T>C Likely 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/ush1c-p-pro668 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown