Is MYO7A p.Arg302Cys (c.904C>T) pathogenic?

MYO7A p.Arg302Cys (c.904C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.0911); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg302Cys (c.904C>T)?

MYO7A p.Arg302Cys (c.904C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Arg302Cys (c.904C>T) in the general population?

MYO7A p.Arg302Cys (c.904C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg302Cys (c.904C>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

MYO7A p.Arg302Cys

c.904C>T · rs781922871 · VCV504970

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.668	pathogenic-leaning
SaProt	LLR -7.25	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.72, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.9	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 0.015% Admixed American · 9/59,964 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00192% 31/1,613,124 alleles · ultra-rare exomes 24/1,460,904 · genomes 7/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,663
Remaining individualsnot grpmax-eligible	0.00801%	12,488
African / African-American	0.004%	24,977
East Asian	0.00223%	44,872
European (non-Finnish)	0.0011%	90,739

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.Arg302Cys
Coding: c.904C>T
MANE Select: NM_000260
dbSNP: rs781922871
Type: single nucleotide variant
Location: chr11:77158331 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 302: the myosin motor domain; a UniProt-annotated variant site (in)

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.Arg302Gly Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg302His Likely benign ★★★ ⚠ same residue
MYO7A p.Arg302Leu Uncertain significance ★ ⚠ 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

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-arg302cys (accessed [today's date]).

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