Is ILK p.Arg145Ser (c.435A>C) pathogenic?

ILK p.Arg145Ser (c.435A>C) is classified Benign in ILK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). AlphaMissense: ambiguous (0.485); Low-frequency (popmax 2.03%, eas); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Arg145Ser (c.435A>C)?

ILK p.Arg145Ser (c.435A>C) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Arg145Ser (c.435A>C) in the general population?

ILK p.Arg145Ser (c.435A>C) is low-frequency (popmax 2.03%, eas) (gnomAD).

What do computational predictors say about ILK p.Arg145Ser (c.435A>C)?

AlphaMissense predicts ambiguous (score 0.485) — an in-silico prediction, not a clinical call.

ILK p.Arg145Ser

c.435A>C · rs139640491 · VCV201785

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.485 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.03%, eas)

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
AlphaMissense	0.485	ambiguous
REVEL	0.375	indeterminate
SaProt	LLR -6.55	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	GERP 0.56, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	21.9	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 2.03% East Asian · 911/44,878 alleles

Filtering AF 1.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.88%

Overall 0.0583% 941/1,614,018 alleles · low-frequency exomes 881/1,461,748 · genomes 60/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.03%	49
Remaining individualsnot grpmax-eligible	0.0336%	2,976
South Asian	0.00878%	11,386
European (non-Finnish)	8.48e-05%	1,179,902

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.Arg145Ser
Coding: c.435A>C
MANE Select: NM_004517
dbSNP: rs139640491
Type: single nucleotide variant
Location: chr11:6608777 (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-arg145ser (accessed [today's date]).

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