Is CILK1 p.Arg151= (c.453A>G) pathogenic?

CILK1 p.Arg151= (c.453A>G) is classified Likely benign in CILK1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0859%, nfe).

How common is CILK1 p.Arg151= (c.453A>G) in the general population?

CILK1 p.Arg151= (c.453A>G) is ultra-rare (popmax 0.0859%, nfe) (gnomAD).

CILK1 p.Arg151=

c.453A>G · rs149467924 · VCV1144801

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0859%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -5.7, phastCons 0.99
Overall
CADD	9.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0859% European (non-Finnish) · 1,014/1,179,942 alleles

Filtering AF 0.0815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0797%

Overall 0.0668% 1,078/1,614,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0859%	1,164
Admixed American	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.0133%	7,507
Finnishnot grpmax-eligible	0.00156%	64,046

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.Arg151=
Coding: c.453A>G
MANE Select: NM_014920
dbSNP: rs149467924
Type: single nucleotide variant
Location: chr6:53019265 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.47
Residue 151: the protein kinase domain

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

Similar variants

CILK1 p.Arg151Gln Uncertain significance ★★ ⚠ same residue
CILK1 p.Arg151Ter Uncertain significance ★ 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.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-arg151 (accessed [today's date]).

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