Is MYO7A p.Met929Ile (c.2787G>T) pathogenic?

MYO7A p.Met929Ile (c.2787G>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-09). AlphaMissense: ambiguous (0.4037); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Met929Ile (c.2787G>T)?

MYO7A p.Met929Ile (c.2787G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Met929Ile (c.2787G>T) in the general population?

MYO7A p.Met929Ile (c.2787G>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Met929Ile (c.2787G>T)?

AlphaMissense predicts ambiguous (score 0.4037) — an in-silico prediction, not a clinical call.

MYO7A p.Met929Ile

c.2787G>T · rs536410625 · VCV1980769

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4037 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4037	ambiguous
REVEL	0.427	indeterminate
SaProt	LLR -7.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.3	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 0.000424% European (non-Finnish) · 5/1,179,550 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,286 alleles · very rare exomes 4/1,460,030 · genomes 1/152,256 · joint denominator

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.Met929Ile
Coding: c.2787G>T
MANE Select: NM_000260
dbSNP: rs536410625
Type: single nucleotide variant
Location: chr11:77181472 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 929: the 'sah' region

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.Met929Lys Uncertain significance ★ ⚠ same residue
MYO7A p.Met929Thr Uncertain significance ★ ⚠ same residue
MYO7A p.Met929Val 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-met929ile (accessed [today's date]).

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