Is ILK p.His99= (c.297C>T) pathogenic?

ILK p.His99= (c.297C>T) is classified Benign/Likely benign in ILK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 38.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.His99= (c.297C>T)?

ILK p.His99= (c.297C>T) is associated with familial hypertrophic cardiomyopathy (ClinVar).

ILK p.His99=

Q: How common is ILK p.His99= (c.297C>T) in the general population?

ILK p.His99= (c.297C>T) is common (popmax 38.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.297C>T · rs1043388 · VCV137588

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 38.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

familial hypertrophic cardiomyopathy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.42	GERP -3, phastCons 0.19
Overall
CADD	11.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 38.1% African / African-American · 28,557/74,912 alleles

Filtering AF 37.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 37.6%

Overall 26.1% 420,212/1,613,042 alleles · common exomes 375,362/1,460,958 · genomes 44,850/152,084 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	39.9%	3
African / African-Americangrpmax	38.1%	3
East Asian	33.3%	3
Ashkenazi Jewishnot grpmax-eligible	28.9%	3
Middle Eastern	27.9%	4
Remaining individualsnot grpmax-eligible	26.6%	4
European (non-Finnish)	25.4%	4
Finnishnot grpmax-eligible	24.4%	4
South Asian	23%	4
Admixed American	22.2%	5

Amish 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.His99=
Coding: c.297C>T
MANE Select: NM_004517
dbSNP: rs1043388
Type: single nucleotide variant
Location: chr11:6608435 (GRCh38)

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

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-his99 (accessed [today's date]).

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