Is ILK p.Ala124Ser (c.370G>T) pathogenic?

ILK p.Ala124Ser (c.370G>T) is classified Uncertain significance in ILK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.1904); Ultra-rare (popmax 0.066%, mid); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Ala124Ser (c.370G>T)?

ILK p.Ala124Ser (c.370G>T) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Ala124Ser (c.370G>T) in the general population?

ILK p.Ala124Ser (c.370G>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about ILK p.Ala124Ser (c.370G>T)?

AlphaMissense predicts likely benign (score 0.1904) — an in-silico prediction, not a clinical call.

ILK p.Ala124Ser

c.370G>T · rs745709169 · VCV1364215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1904 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

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	0.1904	likely benign
REVEL	0.644	pathogenic-leaning
SaProt	LLR -9.21	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00446% 72/1,613,998 alleles · ultra-rare exomes 64/1,461,714 · genomes 8/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
South Asian	0.022%	4,554
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)	0.00314%	31,888
African / African-American	0.00133%	75,044

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: ILK
Protein: p.Ala124Ser
Coding: c.370G>T
MANE Select: NM_004517
dbSNP: rs745709169
Type: single nucleotide variant
Location: chr11:6608712 (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-ala124ser (accessed [today's date]).

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