Is ILK p.Ala306= (c.918C>T) pathogenic?

ILK p.Ala306= (c.918C>T) is classified Benign in ILK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 26.2%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Ala306= (c.918C>T)?

ILK p.Ala306= (c.918C>T) is associated with familial hypertrophic cardiomyopathy (ClinVar).

ILK p.Ala306=

Q: How common is ILK p.Ala306= (c.918C>T) in the general population?

ILK p.Ala306= (c.918C>T) is common (popmax 26.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.918C>T · rs2292195 · VCV137591

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 26.2%, nfe) — 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 2.3	GERP -1.7, phastCons 1
Overall
CADD	11.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.2% European (non-Finnish) · 309,583/1,179,946 alleles

Filtering AF 26.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.1%

Overall 24.6% 396,520/1,613,950 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	29.2%	3
European (non-Finnish)grpmax	26.2%	4
Ashkenazi Jewishnot grpmax-eligible	24.9%	4
Admixed American	23%	4
Remaining individualsnot grpmax-eligible	23%	4
Middle Eastern	21.1%	5
South Asian	16.3%	6
African / African-American	14.7%	7
Amishnot grpmax-eligible	13.9%	7
East Asian	12.1%	8

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala306=
Coding: c.918C>T
MANE Select: NM_004517
dbSNP: rs2292195
Type: single nucleotide variant
Location: chr11:6609785 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 17 PDB
Residue 306: the protein kinase domain; 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.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
ILK p.Arg436Gln Uncertain significance ★★ ⚠ same condition
ILK p.Arg46Cys Uncertain significance ★★ ⚠ same condition
ILK p.Arg59Trp 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-ala306 (accessed [today's date]).

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