Is MYO7A p.Arg1213Trp (c.3637C>T) pathogenic?

MYO7A p.Arg1213Trp (c.3637C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-01-04). AlphaMissense: ambiguous (0.4809); Very rare (popmax 0.00183%, nfe).

How common is MYO7A p.Arg1213Trp (c.3637C>T) in the general population?

MYO7A p.Arg1213Trp (c.3637C>T) is very rare (popmax 0.00183%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg1213Trp (c.3637C>T)?

AlphaMissense predicts ambiguous (score 0.4809) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1213Trp

c.3637C>T · rs772481987 · VCV2181095

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00183%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4809	ambiguous
REVEL	0.721	pathogenic-leaning
SaProt	LLR -10.96	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP 0.52, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.8	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 0.00183% European (non-Finnish) · 21/1,147,064 alleles

Filtering AF 0.00118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000998%

Overall 0.00142% 22/1,549,696 alleles · very rare exomes 19/1,397,480 · genomes 3/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00183%	54,622
South Asian	0.0012%	83,670

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.Arg1213Trp
Coding: c.3637C>T
MANE Select: NM_000260
dbSNP: rs772481987
Type: single nucleotide variant
Location: chr11:77190026 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1213: the myth4 1 domain

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

Similar variants

MYO7A p.Arg1213Gln Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg1213Gly Uncertain significance ★ ⚠ same residue
MYO7A p.Arg1213= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type

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-arg1213trp (accessed [today's date]).

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