USH2A p.Pro2241=
c.6723C>T · rs1238280246 · VCV1648134
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00119%, nfe)
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 -12 | GERP -4.9 |
| Overall | ||
| CADD | 0.691 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00119%
European (non-Finnish) · 14/1,179,986 alleles
Filtering AF
0.000688%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.000867%
14/1,613,898 alleles · very rare
exomes 12/1,461,808 · genomes 2/152,090 · joint denominator
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.Pro2241=
- Coding
- c.6723C>T
- MANE Select
- NM_206933
- dbSNP
- rs1238280246
- Type
- single nucleotide variant
- Location
- chr1:215993102 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- USH2A p.Pro2241Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
- USH2A p.Pro2241His Likely pathogenic ★ same residue
- USH2A p.Pro2241Thr Likely pathogenic ★ same residue
- USH2A p.Pro2241Ser Conflicting classifications of pathogenicity ★ same residue
- USH2A p.Pro2241Ala 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
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-pro2241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown