Is MYO7A p.Arg911Trp (c.2731C>T) pathogenic?

MYO7A p.Arg911Trp (c.2731C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.1669); Very rare (popmax 0.00687%, eas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg911Trp (c.2731C>T)?

MYO7A p.Arg911Trp (c.2731C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Arg911Trp (c.2731C>T) in the general population?

MYO7A p.Arg911Trp (c.2731C>T) is very rare (popmax 0.00687%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg911Trp (c.2731C>T)?

AlphaMissense predicts likely benign (score 0.1669) — an in-silico prediction, not a clinical call.

MYO7A p.Arg911Trp

c.2731C>T · rs377072368 · VCV1313139

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00687%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1669	likely benign
REVEL	0.598	indeterminate
SaProt	LLR -11.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	28.8	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 0.00687% East Asian · 3/43,654 alleles

Filtering AF 0.00182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000905%

Overall 0.00107% 17/1,586,912 alleles · very rare exomes 15/1,434,694 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00687%	14,551
Remaining individualsnot grpmax-eligible	0.00325%	30,772
Finnishnot grpmax-eligible	0.00164%	61,044
African / African-American	0.00134%	74,440
European (non-Finnish)	0.000857%	116,742

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.Arg911Trp
Coding: c.2731C>T
MANE Select: NM_000260
dbSNP: rs377072368
Type: single nucleotide variant
Location: chr11:77181416 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 911: the 'sah' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg911Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala162Thr Uncertain significance ★★ ⚠ 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-arg911trp (accessed [today's date]).

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