Is MYO7A p.Val382Leu (c.1144G>T) pathogenic?

MYO7A p.Val382Leu (c.1144G>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-12). AlphaMissense: likely pathogenic (0.9713); Very rare (popmax 0.000172%, nfe); Associated with hearing loss disorder.

What condition is associated with MYO7A p.Val382Leu (c.1144G>T)?

MYO7A p.Val382Leu (c.1144G>T) is associated with hearing loss disorder (ClinVar).

How common is MYO7A p.Val382Leu (c.1144G>T) in the general population?

MYO7A p.Val382Leu (c.1144G>T) is very rare (popmax 0.000172%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Val382Leu (c.1144G>T)?

AlphaMissense predicts likely pathogenic (score 0.9713) — an in-silico prediction, not a clinical call.

MYO7A p.Val382Leu

c.1144G>T · rs782440130 · VCV1065063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9713 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.9713	likely pathogenic
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -7.17	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 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.7	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 0.000172% European (non-Finnish) · 2/1,164,516 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,581,542 alleles · very rare exomes 1/1,429,348 · genomes 1/152,194 · joint denominator

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.Val382Leu
Coding: c.1144G>T
MANE Select: NM_000260
dbSNP: rs782440130
Type: single nucleotide variant
Location: chr11:77160226 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 382: the myosin motor domain

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

Disease context

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Val382Ala Uncertain significance ★ ⚠ same residue
MYO7A p.Val382= Likely benign ★ same residue
MYO7A c.4442-1G>C Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala598Thr Uncertain significance ★★ same condition
MYO7A p.Ala889Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg1967Gln Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg467Trp 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-val382leu (accessed [today's date]).

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