Is MYO7A p.Ile592Met (c.1776C>G) pathogenic?

MYO7A p.Ile592Met (c.1776C>G) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-16). AlphaMissense: ambiguous (0.5029); Absent from gnomAD v4.1.

How common is MYO7A p.Ile592Met (c.1776C>G) in the general population?

MYO7A p.Ile592Met (c.1776C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Ile592Met (c.1776C>G)?

AlphaMissense predicts ambiguous (score 0.5029) — an in-silico prediction, not a clinical call.

MYO7A p.Ile592Met

c.1776C>G · rs781946898 · VCV2108831

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5029 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5029	ambiguous
REVEL	0.481	indeterminate
SaProt	LLR -8.63	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.39	GERP -0.51, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	19.35	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

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.Ile592Met
Coding: c.1776C>G
MANE Select: NM_000260
dbSNP: rs781946898
Type: single nucleotide variant
Location: chr11:77166141 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 592: the myosin motor domain

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

Similar variants

MYO7A p.Ile592Thr Uncertain significance ★★ ⚠ same residue
MYO7A p.Ile592= 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
MYO7A p.Arg853His Likely 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-ile592met (accessed [today's date]).

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