Is CILK1 p.Pro610Ser (c.1828C>T) pathogenic?

CILK1 p.Pro610Ser (c.1828C>T) is classified Uncertain significance in CILK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely benign (0.0921); Very rare (popmax 0.00891%, eas); Associated with CILK1-related disorder.

What condition is associated with CILK1 p.Pro610Ser (c.1828C>T)?

CILK1 p.Pro610Ser (c.1828C>T) is associated with CILK1-related disorder (ClinVar).

How common is CILK1 p.Pro610Ser (c.1828C>T) in the general population?

CILK1 p.Pro610Ser (c.1828C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CILK1 p.Pro610Ser (c.1828C>T)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

CILK1 p.Pro610Ser

c.1828C>T · VCV3347312

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CILK1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 36 kb · p 7.8e-05 · regional, not allelic
Overall
CADD	21.3	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 0.00891% East Asian · 4/44,882 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000342% 5/1,461,876 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
European (non-Finnish)	8.47e-05%	1,180,025

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.Pro610Ser
Coding: c.1828C>T
MANE Select: NM_014920
Type: single nucleotide variant
Location: chr6:53005220 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.47
Residue 610: the 'disordered' region

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

Disease context

CILK1-related disorder

Similar variants

CILK1 p.Pro610= Likely benign ★ same residue
CILK1 p.Arg49Trp Uncertain significance ★ ⚠ same condition
CILK1 p.Phe115Cys Uncertain significance ★ ⚠ same condition
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

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-pro610ser (accessed [today's date]).

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