Is ILK p.Met425Leu (c.1273A>C) pathogenic?

ILK p.Met425Leu (c.1273A>C) is classified Uncertain significance in ILK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: ambiguous (0.4074); No allele count reported in gnomAD v4.1 (AN 1,614,216); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Met425Leu (c.1273A>C)?

ILK p.Met425Leu (c.1273A>C) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Met425Leu (c.1273A>C) in the general population?

ILK p.Met425Leu (c.1273A>C) is no allele count reported in gnomAD v4.1 (AN 1,614,216) (gnomAD).

What do computational predictors say about ILK p.Met425Leu (c.1273A>C)?

AlphaMissense predicts ambiguous (score 0.4074) — an in-silico prediction, not a clinical call.

ILK p.Met425Leu

c.1273A>C · VCV3657973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4074 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,216)

Conditions

familial hypertrophic cardiomyopathy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.4074	ambiguous
REVEL	0.548	indeterminate
SaProt	LLR -7.25	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	23.1	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

No allele count reported in gnomAD v4.1 (AN 1,614,216). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ILK
Protein: p.Met425Leu
Coding: c.1273A>C
MANE Select: NM_004517
Type: single nucleotide variant
Location: chr11:6610525 (GRCh38)

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

Disease context

familial hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/ilk-p-met425leu (accessed [today's date]).

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