Is MYO7A p.Ala391Val (c.1172C>T) pathogenic?

MYO7A p.Ala391Val (c.1172C>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-14). AlphaMissense: likely pathogenic (0.9521); No allele count reported in gnomAD v4.1 (AN 1,574,714); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Ala391Val (c.1172C>T)?

MYO7A p.Ala391Val (c.1172C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Ala391Val (c.1172C>T) in the general population?

MYO7A p.Ala391Val (c.1172C>T) is no allele count reported in gnomAD v4.1 (AN 1,574,714) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Ala391Val (c.1172C>T)?

AlphaMissense predicts likely pathogenic (score 0.9521) — an in-silico prediction, not a clinical call.

MYO7A p.Ala391Val

c.1172C>T · rs1555067608 · VCV557374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9521 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,574,714)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9521	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -11.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.93	donor gain · deltas
Pangolin	Δ0.72	gain · loss 0.37 · agrees with SpliceAI · independent
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	35.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,574,714). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MYO7A
Protein: p.Ala391Val
Coding: c.1172C>T
MANE Select: NM_000260
dbSNP: rs1555067608
Type: single nucleotide variant
Location: chr11:77160254 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 391: the myosin motor domain

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 2

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Ala391= 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-ala391val (accessed [today's date]).

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