Is MYO7A p.Tyr95Phe (c.284A>T) pathogenic?

MYO7A p.Tyr95Phe (c.284A>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-07-01). AlphaMissense: ambiguous (0.4799); Absent from gnomAD v4.1; Associated with Rare genetic deafness.

What condition is associated with MYO7A p.Tyr95Phe (c.284A>T)?

MYO7A p.Tyr95Phe (c.284A>T) is associated with Rare genetic deafness, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Tyr95Phe (c.284A>T) in the general population?

MYO7A p.Tyr95Phe (c.284A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Tyr95Phe (c.284A>T)?

AlphaMissense predicts ambiguous (score 0.4799) — an in-silico prediction, not a clinical call.

MYO7A p.Tyr95Phe

c.284A>T · rs797044489 · VCV164654

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Rare genetic deafness

Computational evidence

Protein change
AlphaMissense	0.4799	ambiguous
REVEL	0.878	moderately pathogenic-leaning
SaProt	LLR -11.39	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	32.0	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.Tyr95Phe
Coding: c.284A>T
MANE Select: NM_000260
dbSNP: rs797044489
Type: single nucleotide variant
Location: chr11:77147949 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 95: 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

Also linked: autosomal recessive nonsyndromic hearing loss 2

Similar variants

MYO7A p.Tyr95Cys Likely pathogenic ★ same residue
MYO7A p.Tyr95Ter Pathogenic ★ same residue
MYO7A p.Tyr95= Uncertain significance ★ same residue
MYO7A p.Tyr95His Uncertain significance ★ ⚠ same residue
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys 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-tyr95phe (accessed [today's date]).

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