Is ILK p.Cys129Ser (c.386G>C) pathogenic?

ILK p.Cys129Ser (c.386G>C) is classified Uncertain significance in ILK (ClinVar, Single submitter, 1 submitter; last evaluated 2015-11-11). AlphaMissense: likely benign (0.3019); Very rare (popmax 0.000169%, nfe).

How common is ILK p.Cys129Ser (c.386G>C) in the general population?

ILK p.Cys129Ser (c.386G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ILK p.Cys129Ser (c.386G>C)?

AlphaMissense predicts likely benign (score 0.3019) — an in-silico prediction, not a clinical call.

ILK p.Cys129Ser

c.386G>C · rs1332744590 · VCV635243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3019	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,974 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,984 alleles · very rare

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.Cys129Ser
Coding: c.386G>C
MANE Select: NM_004517
dbSNP: rs1332744590
Type: single nucleotide variant
Location: chr11:6608728 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 17 PDB
Residue 129: the 'interaction with lims1' region

Full ILK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ILK p.Cys129= Likely benign ★ same residue
ILK p.Ala41Val Uncertain significance ★★ ⚠ same type
ILK p.Arg149Gln Uncertain significance ★★ ⚠ same type
ILK p.Arg161Cys Uncertain significance ★★ ⚠ same type
ILK p.Arg161His Uncertain significance ★★ ⚠ same type
ILK p.Arg334Gln Uncertain significance ★★ ⚠ same type
ILK p.Arg436Gln Uncertain significance ★★ ⚠ same type
ILK p.Arg46Cys Uncertain significance ★★ ⚠ same type

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-cys129ser (accessed [today's date]).

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