Is MYO7A p.Ala1445Val (c.4334C>T) pathogenic?

MYO7A p.Ala1445Val (c.4334C>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-23). AlphaMissense: likely benign (0.1214); Ultra-rare (popmax 0.0135%, eas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ala1445Val (c.4334C>T)?

MYO7A p.Ala1445Val (c.4334C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Ala1445Val (c.4334C>T) in the general population?

MYO7A p.Ala1445Val (c.4334C>T) is ultra-rare (popmax 0.0135%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Ala1445Val (c.4334C>T)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

MYO7A p.Ala1445Val

c.4334C>T · VCV4840290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.8	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 0.0135% East Asian · 6/44,356 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00398%

Overall 0.000438% 7/1,597,826 alleles · ultra-rare exomes 7/1,445,512 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0135%	7,393
South Asian	0.00114%	88,058

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.Ala1445Val
Coding: c.4334C>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77197491 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1445: 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

Similar variants

MYO7A p.Ala1445Thr Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1445Asp Uncertain significance ★ ⚠ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ 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-ala1445val (accessed [today's date]).

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