Is MYO7A p.Arg634Gln (c.1901G>A) pathogenic?

MYO7A p.Arg634Gln (c.1901G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-02). AlphaMissense: likely pathogenic (0.9829); Very rare (popmax 0.00645%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg634Gln (c.1901G>A)?

MYO7A p.Arg634Gln (c.1901G>A) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg634Gln (c.1901G>A) in the general population?

MYO7A p.Arg634Gln (c.1901G>A) is very rare (popmax 0.00645%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg634Gln (c.1901G>A)?

AlphaMissense predicts likely pathogenic (score 0.9829) — an in-silico prediction, not a clinical call.

MYO7A p.Arg634Gln

c.1901G>A · rs781812509 · VCV802706

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9829 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00645%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.9829	likely pathogenic
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -10.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00645% European (non-Finnish) · 74/1,147,306 alleles

Filtering AF 0.00525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00481%

Overall 0.00535% 83/1,552,036 alleles · very rare exomes 78/1,399,790 · genomes 5/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00645%	15,504
African / African-American	0.00547%	18,272
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,646
Remaining individualsnot grpmax-eligible	0.00333%	30,071
South Asian	0.00238%	42,035

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: MYO7A
Protein: p.Arg634Gln
Coding: c.1901G>A
MANE Select: NM_000260
dbSNP: rs781812509
Type: single nucleotide variant
Location: chr11:77172851 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 634: the myosin motor domain; the 'actin-binding' region

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1B

Similar variants

MYO7A p.Arg634Ter Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Arg634= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His 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/myo7a-p-arg634gln (accessed [today's date]).

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