Is MYO7A p.Ala1551Val (c.4652C>T) pathogenic?

MYO7A p.Ala1551Val (c.4652C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-18). AlphaMissense: likely benign (0.0875); Very rare (popmax 0.00383%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ala1551Val (c.4652C>T)?

MYO7A p.Ala1551Val (c.4652C>T) is associated with Inborn genetic diseases, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Ala1551Val (c.4652C>T) in the general population?

MYO7A p.Ala1551Val (c.4652C>T) is very rare (popmax 0.00383%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Ala1551Val (c.4652C>T)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

MYO7A p.Ala1551Val

c.4652C>T · rs756854177 · VCV1120132

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00383%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.94, phastCons 0.012
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	15.5	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 0.00383% European (non-Finnish) · 45/1,176,458 alleles

Filtering AF 0.00292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00299% 48/1,604,890 alleles · very rare exomes 47/1,452,676 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00383%	26,144
East Asian	0.00224%	44,620
African / African-American	0.00134%	74,818
South Asian	0.00112%	89,144

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.Ala1551Val
Coding: c.4652C>T
MANE Select: NM_000260
dbSNP: rs756854177
Type: single nucleotide variant
Location: chr11:77199618 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1551: the ferm 1 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.Ala1551= Likely benign ★ 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
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp Likely 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-ala1551val (accessed [today's date]).

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