Is MYO7A p.Asp365Ala (c.1094A>C) pathogenic?

MYO7A p.Asp365Ala (c.1094A>C) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-16). AlphaMissense: likely benign (0.1667); Very rare (popmax 0.00545%, afr).

How common is MYO7A p.Asp365Ala (c.1094A>C) in the general population?

MYO7A p.Asp365Ala (c.1094A>C) is very rare (popmax 0.00545%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Asp365Ala (c.1094A>C)?

AlphaMissense predicts likely benign (score 0.1667) — an in-silico prediction, not a clinical call.

MYO7A p.Asp365Ala

c.1094A>C · rs924913478 · VCV870796

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00545%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1667	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP -0.72, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.0	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 0.00545% African / African-American · 4/73,432 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000256% 4/1,562,994 alleles · very rare exomes 3/1,410,826 · genomes 1/152,168 · 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.Asp365Ala
Coding: c.1094A>C
MANE Select: NM_000260
dbSNP: rs924913478
Type: single nucleotide variant
Location: chr11:77160176 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 365: the myosin motor domain

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

Similar variants

MYO7A p.Asp365= Likely benign ★ same residue
MYO7A p.Asp365fs Pathogenic ★★ 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

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-asp365ala (accessed [today's date]).

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