Is USH2A p.Pro2502= (c.7506G>A) pathogenic?

USH2A p.Pro2502= (c.7506G>A) is classified Benign in USH2A (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 9.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with USH2A p.Pro2502= (c.7506G>A)?

USH2A p.Pro2502= (c.7506G>A) is associated with inherited retinal dystrophy, Usher syndrome type 2A (ClinVar).

USH2A p.Pro2502=

Q: How common is USH2A p.Pro2502= (c.7506G>A) in the general population?

USH2A p.Pro2502= (c.7506G>A) is common (popmax 9.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7506G>A · rs12404427 · VCV48584

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 9.1%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

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 -16	GERP -5.5
Overall
CADD	1.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.1% European (non-Finnish) · 107,341/1,179,634 alleles

Filtering AF 9.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.03%

Overall 8.27% 133,465/1,613,400 alleles · common exomes 121,987/1,461,328 · genomes 11,478/152,072 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	9.1%	11
Admixed American	8.98%	11
African / African-American	8.13%	12
Remaining individualsnot grpmax-eligible	7.36%	14
Amishnot grpmax-eligible	6.15%	16
South Asian	5.8%	17
Finnishnot grpmax-eligible	5.18%	19
Ashkenazi Jewishnot grpmax-eligible	3.95%	25
Middle Eastern	3.28%	30
East Asian	0.078%	1,281

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.Pro2502=
Coding: c.7506G>A
MANE Select: NM_206933
dbSNP: rs12404427
Type: single nucleotide variant
Location: chr1:215900163 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2502: the fibronectin type-iii 11 domain

Full USH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 2A

Similar variants

USH2A p.Pro2502Leu Uncertain significance ★ same residue
USH2A c.12295-3T>A Pathogenic ★★★ same condition
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

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-pro2502 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown