Is CMPK1 p.Arg6Leu (c.17G>T) pathogenic?

CMPK1 p.Arg6Leu (c.17G>T) is classified Uncertain significance in CMPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). Very rare (popmax 0.000901%, nfe).

How common is CMPK1 p.Arg6Leu (c.17G>T) in the general population?

CMPK1 p.Arg6Leu (c.17G>T) is very rare (popmax 0.000901%, nfe) (gnomAD).

CMPK1 p.Arg6Leu

c.17G>T · VCV4230475

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000901%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.082	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -1.8
Regional constraint	o/e 1.31	unconstrained · MANE · 100 bp · p 0.038 · regional, not allelic
Overall
CADD	3.593	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000901% European (non-Finnish) · 10/1,109,628 alleles

Filtering AF 0.000456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000332%

Overall 0.00075% 10/1,333,474 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: CMPK1
Protein: p.Arg6Leu
Coding: c.17G>T
MANE Select: NM_016308
Type: single nucleotide variant
Location: chr1:47333962 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 97.06 · 2 PDB
Residue 6: a β-strand

Full CMPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMPK1 p.Arg54Leu Uncertain significance ★ same type
CMPK1 p.Asn156Ser Uncertain significance ★ same type
CMPK1 p.Glu178Lys Uncertain significance ★ same type
CMPK1 p.Gly43Cys Uncertain significance ★ same type
CMPK1 p.Ile207Val Uncertain significance ★ same type
CMPK1 p.Leu10Phe Uncertain significance ★ same type
CMPK1 p.Pro24Thr Uncertain significance ★ same type
CMPK1 p.Ser147Pro 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/cmpk1-p-arg6leu (accessed [today's date]).

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