Is MYO7A p.Arg921Trp (c.2761C>T) pathogenic?

MYO7A p.Arg921Trp (c.2761C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-23). AlphaMissense: likely benign (0.1662); Ultra-rare (popmax 0.0253%, afr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg921Trp (c.2761C>T)?

MYO7A p.Arg921Trp (c.2761C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg921Trp (c.2761C>T) in the general population?

MYO7A p.Arg921Trp (c.2761C>T) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg921Trp (c.2761C>T)?

AlphaMissense predicts likely benign (score 0.1662) — an in-silico prediction, not a clinical call.

MYO7A p.Arg921Trp

c.2761C>T · rs530696050 · VCV860289

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1662 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.1662	likely benign
REVEL	0.596	indeterminate
SaProt	LLR -12.67	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 -0.78	GERP -0.75, phastCons 0.002
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.5	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 0.0253% African / African-American · 19/74,970 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00249% 40/1,606,284 alleles · ultra-rare exomes 29/1,453,958 · genomes 11/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,946
East Asian	0.00448%	22,317
Remaining individualsnot grpmax-eligible	0.00321%	31,115
European (non-Finnish)	0.00136%	73,555
South Asian	0.00112%	89,640

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.Arg921Trp
Coding: c.2761C>T
MANE Select: NM_000260
dbSNP: rs530696050
Type: single nucleotide variant
Location: chr11:77181446 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 921: the 'sah' region

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

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg921Gln 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-arg921trp (accessed [today's date]).

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