USH2A p.Ser4530=
c.13590A>G · rs1343900269 · VCV1654194
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
inherited retinal dystrophy
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 -5.3 | GERP -3 |
| Overall | ||
| CADD | 0.261 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,852 alleles
Overall
0.000124%
2/1,613,990 alleles · very rare
exomes 2/1,461,804 · genomes 0/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,852 |
| European (non-Finnish) | 8.47e-05% | 1,179,947 |
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.Ser4530=
- Coding
- c.13590A>G
- MANE Select
- NM_206933
- dbSNP
- rs1343900269
- Type
- single nucleotide variant
- Location
- chr1:215674321 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 4530
- the fibronectin type-iii 30 domain; the 'disordered' region
Similar variants
- USH2A p.Ser4530Leu Uncertain significance ★★ same residue
- USH2A c.8559-2A>G Pathogenic ★★★ same condition
- USH2A c.8682-9A>G Pathogenic ★★★ same condition
- USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same condition
- USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same condition
- USH2A p.Arg4192Cys Likely pathogenic ★★★ ⚠ same condition
- USH2A p.Asn346His Pathogenic ★★★ same condition
- USH2A p.Asn4292Asp 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/ush2a-p-ser4530 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown