Is USH2A p.Leu293= (c.879T>G) pathogenic?

USH2A p.Leu293= (c.879T>G) is classified Conflicting classifications of pathogenicity in USH2A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 6.71%, eas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with USH2A p.Leu293= (c.879T>G)?

USH2A p.Leu293= (c.879T>G) is associated with inherited retinal dystrophy, Usher syndrome type 2A, retinitis pigmentosa (ClinVar).

USH2A p.Leu293=

Q: How common is USH2A p.Leu293= (c.879T>G) in the general population?

USH2A p.Leu293= (c.879T>G) is common (popmax 6.71%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.879T>G · rs3767698 · VCV48609

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 6.71%, eas) — 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 -0.3	GERP 0.3, phastCons 0.001
Overall
CADD	2.748	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.71% East Asian · 3,005/44,756 alleles

Filtering AF 6.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.43%

Overall 0.237% 3,826/1,613,342 alleles · common exomes 3,400/1,461,184 · genomes 426/152,158 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	6.71%	15
Admixed American	0.556%	180
South Asian	0.262%	381
Remaining individualsnot grpmax-eligible	0.261%	383
Ashkenazi Jewishnot grpmax-eligible	0.108%	925
African / African-American	0.0333%	2,999
Middle Eastern	0.0165%	6,050
European (non-Finnish)	0.00229%	43,690
Finnishnot grpmax-eligible	0.00156%	64,000

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.Leu293=
Coding: c.879T>G
MANE Select: NM_206933
dbSNP: rs3767698
Type: single nucleotide variant
Location: chr1:216325569 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 293: the laminin n-terminal 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 retinitis pigmentosa

Similar variants

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
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-leu293 (accessed [today's date]).

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