Is CMPK2 p.Pro379Leu (c.1136C>T) pathogenic?

CMPK2 p.Pro379Leu (c.1136C>T) is classified Uncertain significance in CMPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-06). AlphaMissense: likely benign (0.168); Ultra-rare (popmax 0.06%, afr).

How common is CMPK2 p.Pro379Leu (c.1136C>T) in the general population?

CMPK2 p.Pro379Leu (c.1136C>T) is ultra-rare (popmax 0.06%, afr) (gnomAD).

What do computational predictors say about CMPK2 p.Pro379Leu (c.1136C>T)?

AlphaMissense predicts likely benign (score 0.168) — an in-silico prediction, not a clinical call.

CMPK2 p.Pro379Leu

c.1136C>T · rs199649469 · VCV2463126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.168 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.168	likely benign
REVEL	0.68	pathogenic-leaning
SaProt	LLR -9.13	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.06% African / African-American · 45/75,044 alleles

Filtering AF 0.046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0411%

Overall 0.00328% 53/1,614,172 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.06%	1,668
Admixed American	0.00333%	30,008
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000424%	236,006

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: CMPK2
Protein: p.Pro379Leu
Coding: c.1136C>T
MANE Select: NM_207315
dbSNP: rs199649469
Type: single nucleotide variant
Location: chr2:6851540 (GRCh38)
Gene constraint: LOEUF 1.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.26

Full CMPK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMPK2 p.Ala156Thr Uncertain significance ★ ⚠ same type
CMPK2 p.Ala24Gly Uncertain significance ★ ⚠ same type
CMPK2 p.Ala2Val Uncertain significance ★ ⚠ same type
CMPK2 p.Ala49Ser Uncertain significance ★ ⚠ same type
CMPK2 p.Ala49Thr Uncertain significance ★ ⚠ same type
CMPK2 p.Ala4Ser Uncertain significance ★ ⚠ same type
CMPK2 p.Ala4Val Uncertain significance ★ ⚠ same type
CMPK2 p.Ala51Thr 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/cmpk2-p-pro379leu (accessed [today's date]).

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