Is ILK p.Ser276= (c.828C>T) pathogenic?

ILK p.Ser276= (c.828C>T) is classified Benign/Likely benign in ILK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-29). Rare (popmax 0.236%, sas); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Ser276= (c.828C>T)?

ILK p.Ser276= (c.828C>T) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Ser276= (c.828C>T) in the general population?

ILK p.Ser276= (c.828C>T) is rare (popmax 0.236%, sas) (gnomAD).

ILK p.Ser276=

c.828C>T · rs528302756 · VCV3224311

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.236%, sas)

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 -0.27	GERP -3.8, phastCons 0.17
Overall
CADD	7.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.236% South Asian · 215/91,086 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.2%

Overall 0.0141% 228/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.236%	424
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Middle Eastern	0.0165%	6,062
African / African-American	0.00133%	75,024

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.Ser276=
Coding: c.828C>T
MANE Select: NM_004517
dbSNP: rs528302756
Type: single nucleotide variant
Location: chr11:6609611 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 17 PDB
Residue 276: 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.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-ser276 (accessed [today's date]).

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