Is CILK1 p.Val183= (c.549C>T) pathogenic?

CILK1 p.Val183= (c.549C>T) is classified Likely benign in CILK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-17). Very rare (popmax 0.00534%, afr).

How common is CILK1 p.Val183= (c.549C>T) in the general population?

CILK1 p.Val183= (c.549C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

CILK1 p.Val183=

c.549C>T · rs897326020 · VCV1680562

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 6.6	GERP 0.94, phastCons 1
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,934 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,068 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: CILK1
Protein: p.Val183=
Coding: c.549C>T
MANE Select: NM_014920
dbSNP: rs897326020
Type: single nucleotide variant
Location: chr6:53018444 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.47
Residue 183: the protein kinase domain

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

Similar variants

CILK1 p.Val183Ile 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-val183 (accessed [today's date]).

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