Is USH2A p.Val2497= (c.7491G>T) pathogenic?

USH2A p.Val2497= (c.7491G>T) is classified Likely benign in USH2A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0733%, afr); Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Val2497= (c.7491G>T)?

USH2A p.Val2497= (c.7491G>T) is associated with retinitis pigmentosa 39, Usher syndrome type 2A (ClinVar).

How common is USH2A p.Val2497= (c.7491G>T) in the general population?

USH2A p.Val2497= (c.7491G>T) is ultra-rare (popmax 0.0733%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

USH2A p.Val2497=

c.7491G>T · rs142143100 · VCV1087100

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0733%, afr)

Conditions

retinitis pigmentosa 39

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.2	GERP 2.6, phastCons 0.58
Overall
CADD	7.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0733% African / African-American · 55/75,006 alleles

Filtering AF 0.0578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0522%

Overall 0.00359% 58/1,613,676 alleles · ultra-rare exomes 32/1,461,428 · genomes 26/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0733%	1,364
Remaining individualsnot grpmax-eligible	0.0032%	31,237
Admixed American	0.00167%	59,964

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.Val2497=
Coding: c.7491G>T
MANE Select: NM_206933
dbSNP: rs142143100
Type: single nucleotide variant
Location: chr1:215900178 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2497: the fibronectin type-iii 11 domain

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

Disease context

retinitis pigmentosa 39 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 2A

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

USH2A p.Val2497Met 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-val2497 (accessed [today's date]).

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