Is MYO7A p.Lys1331Arg (c.3992A>G) pathogenic?

MYO7A p.Lys1331Arg (c.3992A>G) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-12). AlphaMissense: likely benign (0.2232); Absent from gnomAD v4.1; Associated with hearing loss disorder.

What condition is associated with MYO7A p.Lys1331Arg (c.3992A>G)?

MYO7A p.Lys1331Arg (c.3992A>G) is associated with hearing loss disorder (ClinVar).

How common is MYO7A p.Lys1331Arg (c.3992A>G) in the general population?

MYO7A p.Lys1331Arg (c.3992A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Lys1331Arg (c.3992A>G)?

AlphaMissense predicts likely benign (score 0.2232) — an in-silico prediction, not a clinical call.

MYO7A p.Lys1331Arg

c.3992A>G · rs2135575658 · VCV1064944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2232 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.2232	likely benign
REVEL	0.45	indeterminate
SaProt	LLR -0.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.55, 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

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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Lys1331Arg
Coding: c.3992A>G
MANE Select: NM_000260
dbSNP: rs2135575658
Type: single nucleotide variant
Location: chr11:77192118 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1331: the ferm 1 domain

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

Disease context

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A c.4442-1G>C Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala598Thr Uncertain significance ★★ same condition
MYO7A p.Ala889Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg1967Gln Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg467Trp Uncertain significance ★★ same condition
MYO7A p.Arg796Trp Uncertain significance ★★ ⚠ same condition
MYO7A p.Gln1929Arg 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-lys1331arg (accessed [today's date]).

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