Is MYO7A p.Thr96Met (c.287C>T) pathogenic?

MYO7A p.Thr96Met (c.287C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-08). AlphaMissense: likely pathogenic (0.9243); Ultra-rare (popmax 0.0121%, afr); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Thr96Met (c.287C>T)?

MYO7A p.Thr96Met (c.287C>T) is associated with MYO7A-related disorder (ClinVar).

How common is MYO7A p.Thr96Met (c.287C>T) in the general population?

MYO7A p.Thr96Met (c.287C>T) is ultra-rare (popmax 0.0121%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Thr96Met (c.287C>T)?

AlphaMissense predicts likely pathogenic (score 0.9243) — an in-silico prediction, not a clinical call.

MYO7A p.Thr96Met

c.287C>T · rs781811444 · VCV179974

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9243 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.9243	likely pathogenic
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -12.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
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	27.8	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 0.0121% African / African-American · 9/74,610 alleles

Filtering AF 0.00626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.00113% 18/1,596,774 alleles · ultra-rare exomes 8/1,444,528 · genomes 10/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0121%	8,290
South Asian	0.0034%	29,398
European (non-Finnish)	0.000513%	195,012

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.Thr96Met
Coding: c.287C>T
MANE Select: NM_000260
dbSNP: rs781811444
Type: single nucleotide variant
Location: chr11:77155908 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 96: the myosin motor domain

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

Disease context

MYO7A-related disorder

Similar variants

MYO7A p.Thr96Lys Likely pathogenic ★ same residue
MYO7A p.Thr96= Conflicting classifications of pathogenicity ★ same residue
MYO7A c.133-2A>G Pathogenic ★★ same condition
MYO7A c.1344-2A>G Pathogenic ★★ same condition
MYO7A c.1690+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.18+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.19-1G>A Likely pathogenic ★★ same condition
MYO7A c.2187+1G>A Pathogenic/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-thr96met (accessed [today's date]).

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