Is ILK p.Pro177Ser (c.529C>T) pathogenic?

ILK p.Pro177Ser (c.529C>T) is classified Uncertain significance in ILK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-24). AlphaMissense: likely pathogenic (0.8082); Absent from gnomAD v4.1; Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Pro177Ser (c.529C>T)?

ILK p.Pro177Ser (c.529C>T) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Pro177Ser (c.529C>T) in the general population?

ILK p.Pro177Ser (c.529C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ILK p.Pro177Ser (c.529C>T)?

AlphaMissense predicts likely pathogenic (score 0.8082) — an in-silico prediction, not a clinical call.

ILK p.Pro177Ser

c.529C>T · rs2493768502 · VCV2744716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8082 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.8082	likely pathogenic
REVEL	0.46	indeterminate
SaProt	LLR -4.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ILK
Protein: p.Pro177Ser
Coding: c.529C>T
MANE Select: NM_004517
dbSNP: rs2493768502
Type: single nucleotide variant
Location: chr11:6608964 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 17 PDB

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.Pro177= Likely benign ★ 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
ILK p.Arg436Gln Uncertain significance ★★ ⚠ same condition
ILK p.Arg46Cys 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-pro177ser (accessed [today's date]).

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