Is MYO7A p.Gln655Ter (c.1963C>T) pathogenic?

MYO7A p.Gln655Ter (c.1963C>T) is classified Pathogenic in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-04). Very rare (popmax 0.0017%, amr); Associated with Rare genetic deafness.

What condition is associated with MYO7A p.Gln655Ter (c.1963C>T)?

MYO7A p.Gln655Ter (c.1963C>T) is associated with Rare genetic deafness (ClinVar).

How common is MYO7A p.Gln655Ter (c.1963C>T) in the general population?

MYO7A p.Gln655Ter (c.1963C>T) is very rare (popmax 0.0017%, amr) (gnomAD).

MYO7A p.Gln655Ter

c.1963C>T · rs397516291 · VCV43167

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Conditions

Rare genetic deafness

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 49
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,934 alleles

Overall 6.23e-05% 1/1,606,162 alleles · very rare exomes 0/1,453,924 · genomes 1/152,238 · joint denominator

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.Gln655Ter
Coding: c.1963C>T
MANE Select: NM_000260
dbSNP: rs397516291
Type: single nucleotide variant
Location: chr11:77174783 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 655: the myosin motor 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 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
MYO7A p.Cys705Ter 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-gln655ter (accessed [today's date]).

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