Is MYO7A p.Arg120His (c.359G>A) pathogenic?

MYO7A p.Arg120His (c.359G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-17). AlphaMissense: likely benign (0.1091); Ultra-rare (popmax 0.0651%, amr); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Arg120His (c.359G>A)?

MYO7A p.Arg120His (c.359G>A) is associated with autosomal dominant nonsyndromic hearing loss 11, inherited retinal dystrophy, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg120His (c.359G>A) in the general population?

MYO7A p.Arg120His (c.359G>A) is ultra-rare (popmax 0.0651%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg120His (c.359G>A)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

MYO7A p.Arg120His

c.359G>A · rs369493667 · VCV43214

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0651%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.736	pathogenic-leaning
SaProt	LLR -7.88	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -0.24, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.6	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 0.0651% Admixed American · 39/59,910 alleles

Filtering AF 0.0489% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00521% 84/1,613,166 alleles · ultra-rare exomes 79/1,460,954 · genomes 5/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0651%	1,536
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,862
Remaining individualsnot grpmax-eligible	0.0048%	20,814
South Asian	0.0044%	22,706
European (non-Finnish)	0.0028%	35,747
African / African-American	0.00267%	37,453

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.Arg120His
Coding: c.359G>A
MANE Select: NM_000260
dbSNP: rs369493667
Type: single nucleotide variant
Location: chr11:77155980 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 120: the myosin motor domain

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

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy Usher syndrome type 1B

Similar variants

MYO7A p.Arg120Cys Uncertain significance ★ ⚠ same residue
MYO7A p.Arg120Ser Conflicting classifications of pathogenicity ★ ⚠ 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-arg120his (accessed [today's date]).

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