Is MYO7A p.Ala1445Asp (c.4334C>A) pathogenic?

MYO7A p.Ala1445Asp (c.4334C>A) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely pathogenic (0.7996); Ultra-rare (popmax 0.0631%, eas).

How common is MYO7A p.Ala1445Asp (c.4334C>A) in the general population?

MYO7A p.Ala1445Asp (c.4334C>A) is ultra-rare (popmax 0.0631%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Ala1445Asp (c.4334C>A)?

AlphaMissense predicts likely pathogenic (score 0.7996) — an in-silico prediction, not a clinical call.

MYO7A p.Ala1445Asp

c.4334C>A · rs768022780 · VCV2074413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7996 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0631%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7996	likely pathogenic
REVEL	0.438	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; 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	24.6	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 0.0631% East Asian · 28/44,356 alleles

Filtering AF 0.0448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0386%

Overall 0.00181% 29/1,597,824 alleles · ultra-rare exomes 29/1,445,510 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0631%	1,584
Remaining individualsnot grpmax-eligible	0.00161%	61,990

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.Ala1445Asp
Coding: c.4334C>A
MANE Select: NM_000260
dbSNP: rs768022780
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

Similar variants

MYO7A p.Ala1445Thr Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1445Val Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type
MYO7A p.Arg853His Likely pathogenic ★★★ same type

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-ala1445asp (accessed [today's date]).

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