Is MYO7A p.Ala397Asp (c.1190C>A) pathogenic?

MYO7A p.Ala397Asp (c.1190C>A) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-17). AlphaMissense: likely pathogenic (0.9955); Very rare (popmax 0.00566%, amr); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Ala397Asp (c.1190C>A)?

MYO7A p.Ala397Asp (c.1190C>A) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Ala397Asp (c.1190C>A) in the general population?

MYO7A p.Ala397Asp (c.1190C>A) is very rare (popmax 0.00566%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Ala397Asp (c.1190C>A)?

AlphaMissense predicts likely pathogenic (score 0.9955) — an in-silico prediction, not a clinical call.

MYO7A p.Ala397Asp

c.1190C>A · rs1555067667 · VCV553245

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00566%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.9955	likely pathogenic ✓ concordant with ClinVar · top 8% in MYO7A
REVEL	0.942	strongly pathogenic-leaning
SaProt	LLR -14.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	29.1	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 0.00566% Admixed American · 3/52,992 alleles

Filtering AF 0.0015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000816%

Overall 0.000256% 4/1,563,768 alleles · very rare exomes 2/1,411,578 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00566%	17,664
Remaining individualsnot grpmax-eligible	0.00165%	60,678

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.Ala397Asp
Coding: c.1190C>A
MANE Select: NM_000260
dbSNP: rs1555067667
Type: single nucleotide variant
Location: chr11:77160272 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 397: the myosin motor domain; a UniProt-annotated variant site (in ush1b)

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

Disease context

MYO7A-related disorder

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

Similar variants

MYO7A p.Ala397Thr Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Ala397= Likely benign ★★ same residue
MYO7A p.Ala397Gly Likely pathogenic ★ ⚠ same residue
MYO7A p.Ala397Val Likely pathogenic ★ same residue
MYO7A p.Ala397Ser Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln 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-ala397asp (accessed [today's date]).

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