Is ILK p.Pro273= (c.819G>A) pathogenic?

ILK p.Pro273= (c.819G>A) is classified Benign/Likely benign in ILK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 47.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Pro273= (c.819G>A)?

ILK p.Pro273= (c.819G>A) is associated with familial hypertrophic cardiomyopathy (ClinVar).

ILK p.Pro273=

Q: How common is ILK p.Pro273= (c.819G>A) in the general population?

ILK p.Pro273= (c.819G>A) is common (popmax 47.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.819G>A · rs1043390 · VCV137590

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 47.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -0.28, phastCons 0.94
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.7% African / African-American · 35,699/74,902 alleles

Filtering AF 47.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.1%

Overall 26.7% 430,398/1,613,698 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	47.7%	2
Amishnot grpmax-eligible	39%	3
East Asian	33.3%	3
Middle Eastern	29.7%	3
Ashkenazi Jewishnot grpmax-eligible	29%	3
Remaining individualsnot grpmax-eligible	27.5%	4
European (non-Finnish)	25.5%	4
Finnishnot grpmax-eligible	24.4%	4
South Asian	23.7%	4
Admixed American	22.9%	4

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.Pro273=
Coding: c.819G>A
MANE Select: NM_004517
dbSNP: rs1043390
Type: single nucleotide variant
Location: chr11:6609602 (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.Pro273Arg 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-pro273 (accessed [today's date]).

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