Is MYO7A p.Arg373His (c.1118G>A) pathogenic?

MYO7A p.Arg373His (c.1118G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-02). AlphaMissense: ambiguous (0.3965); Ultra-rare (popmax 0.0203%, afr).

How common is MYO7A p.Arg373His (c.1118G>A) in the general population?

MYO7A p.Arg373His (c.1118G>A) is ultra-rare (popmax 0.0203%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg373His (c.1118G>A)?

AlphaMissense predicts ambiguous (score 0.3965) — an in-silico prediction, not a clinical call.

MYO7A p.Arg373His

c.1118G>A · rs201491278 · VCV2083510

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3965 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, afr)

Computational evidence

Protein change
AlphaMissense	0.3965	ambiguous
REVEL	0.565	indeterminate
SaProt	LLR -11.34	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.4	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 0.0203% African / African-American · 15/73,986 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.00254% 40/1,577,520 alleles · ultra-rare exomes 33/1,425,346 · genomes 7/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0203%	4,932
South Asian	0.00234%	42,789
European (non-Finnish)	0.00189%	52,835
Admixed American	0.00181%	55,126

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.Arg373His
Coding: c.1118G>A
MANE Select: NM_000260
dbSNP: rs201491278
Type: single nucleotide variant
Location: chr11:77160200 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 373: the myosin motor domain

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

Similar variants

MYO7A p.Arg373Gly Likely pathogenic ★ same residue
MYO7A p.Arg373Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg373Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg373= 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

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-arg373his (accessed [today's date]).

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