Is MYO7A p.Arg921Gln (c.2762G>A) pathogenic?

MYO7A p.Arg921Gln (c.2762G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-13). AlphaMissense: likely benign (0.0641); Ultra-rare (popmax 0.0515%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg921Gln (c.2762G>A)?

MYO7A p.Arg921Gln (c.2762G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg921Gln (c.2762G>A) in the general population?

MYO7A p.Arg921Gln (c.2762G>A) is ultra-rare (popmax 0.0515%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg921Gln (c.2762G>A)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

MYO7A p.Arg921Gln

c.2762G>A · rs782498923 · VCV852055

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0515%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.8	GERP -0.65, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0515% East Asian · 23/44,668 alleles

Filtering AF 0.0351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0298%

Overall 0.00255% 41/1,607,094 alleles · ultra-rare exomes 35/1,454,848 · genomes 6/152,246 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0515%	1,942
Admixed American	0.0119%	8,423
African / African-American	0.00668%	14,975
Remaining individualsnot grpmax-eligible	0.00321%	31,123
European (non-Finnish)	0.00034%	294,333

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.Arg921Gln
Coding: c.2762G>A
MANE Select: NM_000260
dbSNP: rs782498923
Type: single nucleotide variant
Location: chr11:77181447 (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.Arg921Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg921gln (accessed [today's date]).

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