Is USH2A p.Arg34Gln (c.101G>A) pathogenic?

USH2A p.Arg34Gln (c.101G>A) is classified Uncertain significance in USH2A (ClinVar, Single submitter, 2 submitters; last evaluated 2020-03-17). AlphaMissense: likely benign (0.0667); Very rare (popmax 0.00017%, nfe); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Arg34Gln (c.101G>A)?

USH2A p.Arg34Gln (c.101G>A) is associated with Usher syndrome type 2A (ClinVar).

How common is USH2A p.Arg34Gln (c.101G>A) in the general population?

USH2A p.Arg34Gln (c.101G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about USH2A p.Arg34Gln (c.101G>A)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

USH2A p.Arg34Gln

c.101G>A · rs2039690682 · VCV1026657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Usher syndrome type 2A

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.2
Regional constraint	o/e 1.05	unconstrained · MANE · 797 kb · p 0.00011 · regional, not allelic
Overall
CADD	7.996	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,392 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,988 alleles · very rare exomes 2/1,460,838 · genomes 0/152,150 · joint denominator

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.Arg34Gln
Coding: c.101G>A
MANE Select: NM_206933
dbSNP: rs2039690682
Type: single nucleotide variant
Location: chr1:216422236 (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

Usher syndrome type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USH2A p.Arg34Ter Pathogenic/Likely pathogenic ★★ same residue
USH2A p.Arg34fs Pathogenic/Likely pathogenic ★★ same residue
USH2A p.Arg34= Likely benign ★ 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

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-arg34gln (accessed [today's date]).

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