Is USH2A p.Val191= (c.573A>G) pathogenic?

USH2A p.Val191= (c.573A>G) is classified Benign in USH2A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 6.14%, afr) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with USH2A p.Val191= (c.573A>G)?

USH2A p.Val191= (c.573A>G) is associated with inherited retinal dystrophy, Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

USH2A p.Val191=

Q: How common is USH2A p.Val191= (c.573A>G) in the general population?

USH2A p.Val191= (c.573A>G) is common (popmax 6.14%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.573A>G · rs73102592 · VCV48540

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 6.14%, afr) — 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 3	GERP 1.6, phastCons 1
Overall
CADD	9.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.14% African / African-American · 4,606/74,970 alleles

Filtering AF 6% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.94%

Overall 0.463% 7,473/1,613,368 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.14%	16
East Asian	3.41%	29
Remaining individualsnot grpmax-eligible	0.765%	131
Middle Eastern	0.595%	168
Admixed American	0.449%	223
South Asian	0.161%	620
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,972
European (non-Finnish)	0.0334%	2,994

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.Val191=
Coding: c.573A>G
MANE Select: NM_206933
dbSNP: rs73102592
Type: single nucleotide variant
Location: chr1:216418592 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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 retinitis pigmentosa 39 retinitis pigmentosa

Similar variants

USH2A p.Val191Ala 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-val191 (accessed [today's date]).

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