Is MYO7A p.Arg2209Gln (c.6626G>A) pathogenic?

MYO7A p.Arg2209Gln (c.6626G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-07-12). AlphaMissense: likely benign (0.1643); Very rare (popmax 0.00906%, amr); Associated with Meniere disease.

What condition is associated with MYO7A p.Arg2209Gln (c.6626G>A)?

MYO7A p.Arg2209Gln (c.6626G>A) is associated with Meniere disease, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg2209Gln (c.6626G>A) in the general population?

MYO7A p.Arg2209Gln (c.6626G>A) is very rare (popmax 0.00906%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg2209Gln (c.6626G>A)?

AlphaMissense predicts likely benign (score 0.1643) — an in-silico prediction, not a clinical call.

MYO7A p.Arg2209Gln

c.6626G>A · rs776881443 · VCV957508

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00906%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Meniere disease

Computational evidence

Protein change
AlphaMissense	0.1643	likely benign
REVEL	0.482	indeterminate
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.3	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00906% Admixed American · 5/55,208 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00222%

Overall 0.00152% 24/1,583,216 alleles · very rare exomes 21/1,431,030 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00906%	11,042
African / African-American	0.00404%	24,757
East Asian	0.0023%	43,398
Finnishnot grpmax-eligible	0.00161%	62,020
South Asian	0.00116%	86,174
European (non-Finnish)	0.00112%	89,590

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.Arg2209Gln
Coding: c.6626G>A
MANE Select: NM_000260
dbSNP: rs776881443
Type: single nucleotide variant
Location: chr11:77214674 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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

Disease context

Meniere disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1B

Similar variants

MYO7A p.Arg2209Trp Uncertain significance ★★ same residue
MYO7A p.Arg2209Pro Uncertain significance ★ ⚠ same residue
MYO7A p.Arg2209= 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

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-arg2209gln (accessed [today's date]).

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