Is CMPK2 p.Gly390Asp (c.1169G>A) pathogenic?

CMPK2 p.Gly390Asp (c.1169G>A) is classified Uncertain significance in CMPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: ambiguous (0.3833); Very rare (popmax 0.00133%, afr).

How common is CMPK2 p.Gly390Asp (c.1169G>A) in the general population?

CMPK2 p.Gly390Asp (c.1169G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CMPK2 p.Gly390Asp (c.1169G>A)?

AlphaMissense predicts ambiguous (score 0.3833) — an in-silico prediction, not a clinical call.

CMPK2 p.Gly390Asp

c.1169G>A · VCV4654721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3833	ambiguous
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -8.34	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic
Overall
CADD	26.5	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 0.00133% African / African-American · 1/74,938 alleles

Overall 0.000186% 3/1,614,118 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,938
South Asian	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,048

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.Gly390Asp
Coding: c.1169G>A
MANE Select: NM_207315
Type: single nucleotide variant
Location: chr2:6851507 (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-gly390asp (accessed [today's date]).

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