Is MYO7A p.Val469Met (c.1405G>A) pathogenic?

MYO7A p.Val469Met (c.1405G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-06-19). AlphaMissense: likely pathogenic (0.8934); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Val469Met (c.1405G>A)?

MYO7A p.Val469Met (c.1405G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Val469Met (c.1405G>A) in the general population?

MYO7A p.Val469Met (c.1405G>A) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Val469Met (c.1405G>A)?

AlphaMissense predicts likely pathogenic (score 0.8934) — an in-silico prediction, not a clinical call.

MYO7A p.Val469Met

c.1405G>A · rs367582237 · VCV1374847

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8934 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8934	likely pathogenic
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -8.63	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	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 0.0107% African / African-American · 8/74,874 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00443% 71/1,601,114 alleles · ultra-rare exomes 63/1,448,788 · genomes 8/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,359
European (non-Finnish)	0.00494%	20,237
East Asian	0.00449%	22,259
Finnishnot grpmax-eligible	0.00316%	31,613
Admixed American	0.00171%	58,362

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.Val469Met
Coding: c.1405G>A
MANE Select: NM_000260
dbSNP: rs367582237
Type: single nucleotide variant
Location: chr11:77162181 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 469: the myosin motor domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Val469= Likely benign ★ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala162Thr 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-val469met (accessed [today's date]).

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