Is USH2A p.Gln684= (c.2052A>G) pathogenic?

USH2A p.Gln684= (c.2052A>G) is classified Conflicting classifications of pathogenicity in USH2A (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-01-31). Rare (popmax 0.614%, sas); Associated with inherited retinal dystrophy.

What condition is associated with USH2A p.Gln684= (c.2052A>G)?

USH2A p.Gln684= (c.2052A>G) is associated with inherited retinal dystrophy, Usher syndrome type 2A, retinitis pigmentosa (ClinVar).

How common is USH2A p.Gln684= (c.2052A>G) in the general population?

USH2A p.Gln684= (c.2052A>G) is rare (popmax 0.614%, sas) (gnomAD).

USH2A p.Gln684=

c.2052A>G · rs111033248 · VCV48482

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.614%, sas)

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 -3.4	GERP -2.8
Overall
CADD	1.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.614% South Asian · 559/91,082 alleles

Filtering AF 0.572% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.555%

Overall 0.118% 1,902/1,614,074 alleles · rare exomes 1,804/1,461,776 · genomes 98/152,298 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.614%	163
European (non-Finnish)	0.103%	969
Remaining individualsnot grpmax-eligible	0.0976%	1,025
Middle Eastern	0.0825%	1,212
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,644
Finnishnot grpmax-eligible	0.0234%	4,269
Admixed American	0.02%	5,001
African / African-American	0.0147%	6,822
East Asian	0.00669%	14,941

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.Gln684=
Coding: c.2052A>G
MANE Select: NM_206933
dbSNP: rs111033248
Type: single nucleotide variant
Location: chr1:216251018 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 684: the laminin egf-like 3 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-gln684 (accessed [today's date]).

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