USH2A p.Pro1684=
c.5052G>A · rs747119023 · VCV1092756
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0472%, sas)
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 -0.85 | GERP -2.1 |
| Overall | ||
| CADD | 5.706 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0472%
South Asian · 43/91,084 alleles
Filtering AF
0.036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0321%
Overall
0.00409%
66/1,613,398 alleles · ultra-rare
exomes 58/1,461,260 · genomes 8/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0472% | 2,118 |
| Middle Eastern | 0.0165% | 6,078 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,790 |
| Admixed American | 0.00668% | 14,972 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,220 |
| African / African-American | 0.00267% | 37,442 |
| Finnishnot grpmax-eligible | 0.00156% | 63,988 |
| European (non-Finnish) | 0.000932% | 107,243 |
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.Pro1684=
- Coding
- c.5052G>A
- MANE Select
- NM_206933
- dbSNP
- rs747119023
- Type
- single nucleotide variant
- Location
- chr1:216084813 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1684
- the laminin g-like 1 domain; a UniProt-annotated variant site (found in a patient with non-syndromic sensorineural hearing loss; uncertain significance)
Similar variants
- USH2A p.Pro1684Leu 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-pro1684 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown