Is MYO7A p.Arg90Trp (c.268C>T) pathogenic?

MYO7A p.Arg90Trp (c.268C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-22). AlphaMissense: likely benign (0.1985); Very rare (popmax 0.00969%, amr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg90Trp (c.268C>T)?

MYO7A p.Arg90Trp (c.268C>T) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg90Trp (c.268C>T) in the general population?

MYO7A p.Arg90Trp (c.268C>T) is very rare (popmax 0.00969%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg90Trp (c.268C>T)?

AlphaMissense predicts likely benign (score 0.1985) — an in-silico prediction, not a clinical call.

MYO7A p.Arg90Trp

c.268C>T · rs781834630 · VCV802702

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00969%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.1985	likely benign
REVEL	0.589	indeterminate
SaProt	LLR -11.67	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.52, phastCons 0.97
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.8	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 0.00969% Admixed American · 5/51,616 alleles

Filtering AF 0.00647% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00599%

Overall 0.00643% 100/1,556,386 alleles · very rare exomes 90/1,404,240 · genomes 10/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00969%	10,323
European (non-Finnish)	0.00782%	12,789
Remaining individualsnot grpmax-eligible	0.00663%	15,092
African / African-American	0.00136%	73,320

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.Arg90Trp
Coding: c.268C>T
MANE Select: NM_000260
dbSNP: rs781834630
Type: single nucleotide variant
Location: chr11:77147933 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 90: the myosin motor domain; a UniProt-annotated variant site (in ush1b)

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 1B

Similar variants

MYO7A p.Arg90Gln 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
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp 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-arg90trp (accessed [today's date]).

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