Is MYO7A p.Ala353Val (c.1058C>T) pathogenic?

MYO7A p.Ala353Val (c.1058C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-12). AlphaMissense: likely benign (0.0761); Ultra-rare (popmax 0.0161%, eas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ala353Val (c.1058C>T)?

MYO7A p.Ala353Val (c.1058C>T) is associated with Inborn genetic diseases, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Ala353Val (c.1058C>T) in the general population?

MYO7A p.Ala353Val (c.1058C>T) is ultra-rare (popmax 0.0161%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Ala353Val (c.1058C>T)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

MYO7A p.Ala353Val

c.1058C>T · rs557302067 · VCV955733

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.8	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 0.0161% East Asian · 7/43,386 alleles

Filtering AF 0.00748% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00529%

Overall 0.000504% 8/1,588,446 alleles · ultra-rare exomes 6/1,437,766 · genomes 2/150,680 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0161%	6,198
European (non-Finnish)	8.59e-05%	1,163,586

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.Ala353Val
Coding: c.1058C>T
MANE Select: NM_000260
dbSNP: rs557302067
Type: single nucleotide variant
Location: chr11:77159501 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 353: 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

Also linked: Usher syndrome type 1B

Similar variants

MYO7A p.Ala353= Likely benign ★ same residue
MYO7A p.Ala353_Thr354insTer Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Ala353Thr Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys 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-ala353val (accessed [today's date]).

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