Is MYO7A p.Gly404Arg (c.1210G>A) pathogenic?

MYO7A p.Gly404Arg (c.1210G>A) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). AlphaMissense: likely pathogenic (0.9964); Very rare (popmax 0.00562%, sas).

How common is MYO7A p.Gly404Arg (c.1210G>A) in the general population?

MYO7A p.Gly404Arg (c.1210G>A) is very rare (popmax 0.00562%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Gly404Arg (c.1210G>A)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

MYO7A p.Gly404Arg

c.1210G>A · rs782022331 · VCV2146018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00562%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 6% in MYO7A
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -11.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.96	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	35.0	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 0.00562% South Asian · 5/88,994 alleles

Filtering AF 0.00214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00139%

Overall 0.000499% 8/1,603,680 alleles · very rare exomes 7/1,451,664 · genomes 1/152,016 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00562%	17,799
Finnishnot grpmax-eligible	0.00158%	63,274
European (non-Finnish)	0.00017%	587,848

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.Gly404Arg
Coding: c.1210G>A
MANE Select: NM_000260
dbSNP: rs782022331
Type: single nucleotide variant
Location: chr11:77160982 (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

Similar variants

MYO7A p.Gly404Glu Likely pathogenic ★ ⚠ same residue
MYO7A p.Gly404Trp Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type
MYO7A p.Arg853His Likely pathogenic ★★★ same type

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-gly404arg (accessed [today's date]).

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