Is CMPK1 p.Leu10Phe (c.28C>T) pathogenic?

CMPK1 p.Leu10Phe (c.28C>T) is classified Uncertain significance in CMPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). Very rare (popmax 0.00604%, nfe).

How common is CMPK1 p.Leu10Phe (c.28C>T) in the general population?

CMPK1 p.Leu10Phe (c.28C>T) is very rare (popmax 0.00604%, nfe) (gnomAD).

CMPK1 p.Leu10Phe

c.28C>T · VCV4004026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00604%, 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 0.49	GERP 0.59, phastCons 0.063
Regional constraint	o/e 1.31	unconstrained · MANE · 100 bp · p 0.038 · regional, not allelic
Overall
CADD	18.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00604% European (non-Finnish) · 68/1,125,094 alleles

Filtering AF 0.00484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00443%

Overall 0.00483% 73/1,510,932 alleles · very rare exomes 66/1,359,512 · genomes 7/151,420 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00604%	16,545
African / African-American	0.00431%	23,207
Admixed American	0.00195%	51,178
Remaining individualsnot grpmax-eligible	0.00175%	57,136

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.Leu10Phe
Coding: c.28C>T
MANE Select: NM_016308
Type: single nucleotide variant
Location: chr1:47333973 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 97.06 · 2 PDB

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.Arg6Leu 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.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-leu10phe (accessed [today's date]).

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