Is MYO7A p.Arg1213Gln (c.3638G>A) pathogenic?

MYO7A p.Arg1213Gln (c.3638G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-08). AlphaMissense: likely benign (0.156); Ultra-rare (popmax 0.0131%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg1213Gln (c.3638G>A)?

MYO7A p.Arg1213Gln (c.3638G>A) is associated with Inborn genetic diseases, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg1213Gln (c.3638G>A) in the general population?

MYO7A p.Arg1213Gln (c.3638G>A) is ultra-rare (popmax 0.0131%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg1213Gln (c.3638G>A)?

AlphaMissense predicts likely benign (score 0.156) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1213Gln

c.3638G>A · rs372642675 · VCV881771

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.156 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0131%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.156	likely benign
REVEL	0.453	indeterminate
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.8	GERP -0.72, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	32.0	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 0.0131% South Asian · 11/83,838 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00562%

Overall 0.00135% 21/1,550,982 alleles · ultra-rare exomes 20/1,398,760 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0131%	7,622
Remaining individualsnot grpmax-eligible	0.00833%	12,002
African / African-American	0.00137%	73,238
European (non-Finnish)	0.000349%	286,937

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.Arg1213Gln
Coding: c.3638G>A
MANE Select: NM_000260
dbSNP: rs372642675
Type: single nucleotide variant
Location: chr11:77190027 (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

Disease context

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

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11

Similar variants

MYO7A p.Arg1213Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg1213Gly Uncertain significance ★ ⚠ same residue
MYO7A p.Arg1213= Likely benign ★ 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

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-arg1213gln (accessed [today's date]).

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