Is ILK p.Arg151Trp (c.451C>T) pathogenic?

ILK p.Arg151Trp (c.451C>T) is classified Uncertain significance in ILK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-29). AlphaMissense: ambiguous (0.3574); Very rare (popmax 0.00768%, sas); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Arg151Trp (c.451C>T)?

ILK p.Arg151Trp (c.451C>T) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Arg151Trp (c.451C>T) in the general population?

ILK p.Arg151Trp (c.451C>T) is very rare (popmax 0.00768%, sas) (gnomAD).

What do computational predictors say about ILK p.Arg151Trp (c.451C>T)?

AlphaMissense predicts ambiguous (score 0.3574) — an in-silico prediction, not a clinical call.

ILK p.Arg151Trp

c.451C>T · rs771485363 · VCV966619

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3574 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

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	0.3574	ambiguous
REVEL	0.371	indeterminate
SaProt	LLR -10.80	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	25.9	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 0.00768% South Asian · 7/91,088 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000991% 16/1,614,006 alleles · very rare exomes 15/1,461,838 · genomes 1/152,168 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.000508%	196,667

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.Arg151Trp
Coding: c.451C>T
MANE Select: NM_004517
dbSNP: rs771485363
Type: single nucleotide variant
Location: chr11:6608886 (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-arg151trp (accessed [today's date]).

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