Is MYO7A p.Gln1178Pro (c.3533A>C) pathogenic?

MYO7A p.Gln1178Pro (c.3533A>C) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2010-02-09). AlphaMissense: likely pathogenic (0.9925); Absent from gnomAD v4.1; Associated with Rare genetic deafness.

What condition is associated with MYO7A p.Gln1178Pro (c.3533A>C)?

MYO7A p.Gln1178Pro (c.3533A>C) is associated with Rare genetic deafness (ClinVar).

How common is MYO7A p.Gln1178Pro (c.3533A>C) in the general population?

MYO7A p.Gln1178Pro (c.3533A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Gln1178Pro (c.3533A>C)?

AlphaMissense predicts likely pathogenic (score 0.9925) — an in-silico prediction, not a clinical call.

MYO7A p.Gln1178Pro

c.3533A>C · rs111033482 · VCV43210

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9925 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Rare genetic deafness

Computational evidence

Protein change
AlphaMissense	0.9925	likely pathogenic ✓ concordant with ClinVar
REVEL	0.982	strongly pathogenic-leaning
SaProt	LLR -13.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Gln1178Pro
Coding: c.3533A>C
MANE Select: NM_000260
dbSNP: rs111033482
Type: single nucleotide variant
Location: chr11:77189373 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1178: the myth4 1 domain

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

Disease context

Rare genetic deafness — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Gln1178fs Pathogenic/Likely pathogenic ★★ same residue
MYO7A c.1200+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.2094+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.2283-1G>T Pathogenic ★★ same condition
MYO7A c.285+2T>C Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.4442-2A>C Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala26Glu Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Arg83Ser 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-gln1178pro (accessed [today's date]).

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