Is CILK1 p.Ser17Phe (c.50C>T) pathogenic?

CILK1 p.Ser17Phe (c.50C>T) is classified Uncertain significance in CILK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-14). AlphaMissense: likely pathogenic (0.7061); Ultra-rare (popmax 0.0178%, eas).

How common is CILK1 p.Ser17Phe (c.50C>T) in the general population?

CILK1 p.Ser17Phe (c.50C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CILK1 p.Ser17Phe (c.50C>T)?

AlphaMissense predicts likely pathogenic (score 0.7061) — an in-silico prediction, not a clinical call.

CILK1 p.Ser17Phe

c.50C>T · VCV3607008

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7061	likely pathogenic
REVEL	0.516	indeterminate
SaProt	LLR -15.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 36 kb · p 7.8e-05 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0178% East Asian · 8/44,878 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00109% 16/1,461,738 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,610
European (non-Finnish)	0.000678%	147,493

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: CILK1
Protein: p.Ser17Phe
Coding: c.50C>T
MANE Select: NM_014920
Type: single nucleotide variant
Location: chr6:53041187 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.47
Residue 17: the protein kinase domain; a binding site

Full CILK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CILK1 p.Ser17= Likely benign ★★ same residue
CILK1 c.1344-4T>A Uncertain significance ★★ same type
CILK1 p.Ala629Thr Uncertain significance ★★ ⚠ same type
CILK1 p.Arg124Gln Uncertain significance ★★ ⚠ same type
CILK1 p.Arg151Gln Uncertain significance ★★ ⚠ same type
CILK1 p.Arg262Lys Uncertain significance ★★ ⚠ same type
CILK1 p.Arg280Gln Uncertain significance ★★ ⚠ same type
CILK1 p.Arg332Gln 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/cilk1-p-ser17phe (accessed [today's date]).

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