Is MYO7A p.Gly404Glu (c.1211G>A) pathogenic?

MYO7A p.Gly404Glu (c.1211G>A) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-12). AlphaMissense: likely pathogenic (0.9972); Very rare (popmax 0.00017%, nfe); Associated with hearing loss disorder.

What condition is associated with MYO7A p.Gly404Glu (c.1211G>A)?

MYO7A p.Gly404Glu (c.1211G>A) is associated with hearing loss disorder (ClinVar).

How common is MYO7A p.Gly404Glu (c.1211G>A) in the general population?

MYO7A p.Gly404Glu (c.1211G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Gly404Glu (c.1211G>A)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

MYO7A p.Gly404Glu

c.1211G>A · rs973746837 · VCV1064989

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic ✓ concordant with ClinVar · top 5% in MYO7A
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -5.68	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.86, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,012 alleles

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

Overall 0.000125% 2/1,604,576 alleles · very rare exomes 2/1,452,386 · genomes 0/152,190 · 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: MYO7A
Protein: p.Gly404Glu
Coding: c.1211G>A
MANE Select: NM_000260
dbSNP: rs973746837
Type: single nucleotide variant
Location: chr11:77160983 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 404: the myosin motor domain

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

Disease context

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Gly404Arg Uncertain significance ★ ⚠ same residue
MYO7A p.Gly404Trp Uncertain significance ★ ⚠ same residue
MYO7A c.4442-1G>C Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala598Thr Uncertain significance ★★ same condition
MYO7A p.Ala889Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg1967Gln Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg467Trp Uncertain significance ★★ 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-gly404glu (accessed [today's date]).

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