Is MYO7A p.Arg430His (c.1289G>A) pathogenic?

MYO7A p.Arg430His (c.1289G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-09-01). AlphaMissense: likely benign (0.1455); Very rare (popmax 0.00446%, eas).

How common is MYO7A p.Arg430His (c.1289G>A) in the general population?

MYO7A p.Arg430His (c.1289G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg430His (c.1289G>A)?

AlphaMissense predicts likely benign (score 0.1455) — an in-silico prediction, not a clinical call.

MYO7A p.Arg430His

c.1289G>A · rs782246569 · VCV2201484

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1455	likely benign
REVEL	0.561	indeterminate
SaProt	LLR -5.11	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 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.2	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 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00124% 20/1,613,840 alleles · very rare exomes 18/1,461,678 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
Admixed American	0.00333%	29,999
Remaining individualsnot grpmax-eligible	0.0016%	62,462
African / African-American	0.00133%	74,920
European (non-Finnish)	0.0011%	90,761
South Asian	0.0011%	91,060

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.Arg430His
Coding: c.1289G>A
MANE Select: NM_000260
dbSNP: rs782246569
Type: single nucleotide variant
Location: chr11:77161061 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 430: the myosin motor domain

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

Similar variants

MYO7A p.Arg430Cys Conflicting classifications of pathogenicity ★ ⚠ 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
MYO7A p.Glu968Asp 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-arg430his (accessed [today's date]).

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