USH2A p.Pro4378=
c.13134G>A · rs148975669 · VCV1085550
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00892%, eas)
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 -6.2 | GERP -3.7 |
| Overall | ||
| CADD | 0.686 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
East Asian · 4/44,852 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00173%
28/1,614,052 alleles · very rare
exomes 24/1,461,840 · genomes 4/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00892% | 11,213 |
| South Asian | 0.00769% | 13,010 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| African / African-American | 0.00267% | 37,507 |
| European (non-Finnish) | 0.0011% | 90,770 |
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.Pro4378=
- Coding
- c.13134G>A
- MANE Select
- NM_206933
- dbSNP
- rs148975669
- Type
- single nucleotide variant
- Location
- chr1:215674777 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 4378
- the fibronectin type-iii 29 domain
Similar variants
- USH2A p.Pro4378Gln Uncertain significance ★ same residue
- USH2A p.Pro4378Leu Conflicting classifications of pathogenicity ★ same residue
- USH2A p.Pro4378Ser Uncertain significance ★ same residue
- USH2A p.Pro4378fs Pathogenic/Likely pathogenic ★★ 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
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-pro4378 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown