Is ILK p.Arg149Gln (c.446G>A) pathogenic?

ILK p.Arg149Gln (c.446G>A) is classified Uncertain significance in ILK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.0826); Ultra-rare (popmax 0.0105%, nfe); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Arg149Gln (c.446G>A)?

ILK p.Arg149Gln (c.446G>A) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Arg149Gln (c.446G>A) in the general population?

ILK p.Arg149Gln (c.446G>A) is ultra-rare (popmax 0.0105%, nfe) (gnomAD).

What do computational predictors say about ILK p.Arg149Gln (c.446G>A)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

ILK p.Arg149Gln

c.446G>A · rs869025437 · VCV222652

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% European (non-Finnish) · 124/1,179,596 alleles

Filtering AF 0.00891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00842%

Overall 0.00799% 129/1,613,558 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0105%	9,513
Remaining individualsnot grpmax-eligible	0.0048%	20,823
African / African-American	0.00134%	74,894
South Asian	0.0011%	91,088

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.Arg149Gln
Coding: c.446G>A
MANE Select: NM_004517
dbSNP: rs869025437
Type: single nucleotide variant
Location: chr11:6608788 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 17 PDB
Residue 149: an α-helix

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

Similar variants

ILK p.Ala41Val Uncertain significance ★★ ⚠ same condition
ILK p.Arg161Cys Uncertain significance ★★ ⚠ same condition
ILK p.Arg161His Uncertain significance ★★ ⚠ same condition
ILK p.Arg334Gln Uncertain significance ★★ ⚠ same condition
ILK p.Arg436Gln Uncertain significance ★★ ⚠ same condition
ILK p.Arg46Cys Uncertain significance ★★ ⚠ same condition
ILK p.Arg59Trp Uncertain significance ★★ ⚠ same condition
ILK p.Asn28Ser 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/ilk-p-arg149gln (accessed [today's date]).

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