Is MYO7A p.Arg974Trp (c.2920C>T) pathogenic?

MYO7A p.Arg974Trp (c.2920C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.137); Ultra-rare (popmax 0.029%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg974Trp (c.2920C>T)?

MYO7A p.Arg974Trp (c.2920C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg974Trp (c.2920C>T) in the general population?

MYO7A p.Arg974Trp (c.2920C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg974Trp (c.2920C>T)?

AlphaMissense predicts likely benign (score 0.137) — an in-silico prediction, not a clinical call.

MYO7A p.Arg974Trp

c.2920C>T · rs782582076 · VCV855022

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.137 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.137	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP 0.72, phastCons 0.78
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.029% East Asian · 13/44,858 alleles

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

Overall 0.00316% 51/1,612,848 alleles · ultra-rare exomes 47/1,461,138 · genomes 4/151,710 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,451
Admixed American	0.00667%	14,990
South Asian	0.00439%	22,760
European (non-Finnish)	0.00246%	40,680
Remaining individualsnot grpmax-eligible	0.0016%	62,444

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.Arg974Trp
Coding: c.2920C>T
MANE Select: NM_000260
dbSNP: rs782582076
Type: single nucleotide variant
Location: chr11:77181966 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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.Arg974Gln Uncertain significance ★ ⚠ same residue
MYO7A p.Arg974Leu 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

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-arg974trp (accessed [today's date]).

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