Is ILK p.Pro273Arg (c.818C>G) pathogenic?

ILK p.Pro273Arg (c.818C>G) is classified Likely benign in ILK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-13). AlphaMissense: ambiguous (0.4418); Ultra-rare (popmax 0.0379%, eas); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Pro273Arg (c.818C>G)?

ILK p.Pro273Arg (c.818C>G) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Pro273Arg (c.818C>G) in the general population?

ILK p.Pro273Arg (c.818C>G) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about ILK p.Pro273Arg (c.818C>G)?

AlphaMissense predicts ambiguous (score 0.4418) — an in-silico prediction, not a clinical call.

ILK p.Pro273Arg

c.818C>G · rs774113906 · VCV1093663

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4418 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.4418	ambiguous
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -7.39	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.67	donor gain at this position · masked 0 · deltas
Pangolin	Δ0.25	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	33.0	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 0.0379% East Asian · 17/44,894 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00112% 18/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,641
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Pro273Arg
Coding: c.818C>G
MANE Select: NM_004517
dbSNP: rs774113906
Type: single nucleotide variant
Location: chr11:6609601 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 17 PDB
Residue 273: the protein kinase domain

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.Pro273Gln Uncertain significance ★★ ⚠ same residue
ILK p.Pro273= Benign/Likely benign ★★ same residue
ILK p.Pro273Leu Uncertain significance ★ ⚠ same residue
ILK p.Ala41Val Uncertain significance ★★ ⚠ same condition
ILK p.Arg149Gln 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

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-pro273arg (accessed [today's date]).

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