Is MYO7A p.Arg292Trp (c.874C>T) pathogenic?

MYO7A p.Arg292Trp (c.874C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-24). AlphaMissense: ambiguous (0.4049); Ultra-rare (popmax 0.029%, eas); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg292Trp (c.874C>T)?

MYO7A p.Arg292Trp (c.874C>T) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg292Trp (c.874C>T) in the general population?

MYO7A p.Arg292Trp (c.874C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg292Trp (c.874C>T)?

AlphaMissense predicts ambiguous (score 0.4049) — an in-silico prediction, not a clinical call.

MYO7A p.Arg292Trp

c.874C>T · rs782505601 · VCV306163

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4049 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.4049	ambiguous
REVEL	0.696	pathogenic-leaning
SaProt	LLR -14.33	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 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.7	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 0.029% East Asian · 13/44,782 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00311% 50/1,609,332 alleles · ultra-rare exomes 43/1,457,126 · genomes 7/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,445
Middle Eastern	0.0165%	6,058
Admixed American	0.00669%	14,945
European (non-Finnish)	0.00255%	39,234
Remaining individualsnot grpmax-eligible	0.00161%	62,250
African / African-American	0.00134%	74,862

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.Arg292Trp
Coding: c.874C>T
MANE Select: NM_000260
dbSNP: rs782505601
Type: single nucleotide variant
Location: chr11:77158301 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 292: the myosin motor domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal dominant nonsyndromic hearing loss 11

Similar variants

MYO7A p.Arg292= Likely benign ★★ same residue
MYO7A p.Arg292Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg292Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
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-arg292trp (accessed [today's date]).

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