Is CMPK2 p.His357Gln (c.1071C>A) pathogenic?

CMPK2 p.His357Gln (c.1071C>A) is classified Uncertain significance in CMPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely pathogenic (0.7678); Absent from gnomAD v4.1; Associated with CMPK2-related disorder.

What condition is associated with CMPK2 p.His357Gln (c.1071C>A)?

CMPK2 p.His357Gln (c.1071C>A) is associated with CMPK2-related disorder (ClinVar).

How common is CMPK2 p.His357Gln (c.1071C>A) in the general population?

CMPK2 p.His357Gln (c.1071C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMPK2 p.His357Gln (c.1071C>A)?

AlphaMissense predicts likely pathogenic (score 0.7678) — an in-silico prediction, not a clinical call.

CMPK2 p.His357Gln

c.1071C>A · rs201507613 · VCV2629994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7678 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CMPK2-related disorder

Computational evidence

Protein change
AlphaMissense	0.7678	likely pathogenic
REVEL	0.092	moderately benign-leaning
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic
Overall
CADD	16.84	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CMPK2
Protein: p.His357Gln
Coding: c.1071C>A
MANE Select: NM_207315
dbSNP: rs201507613
Type: single nucleotide variant
Location: chr2:6851605 (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

Disease context

CMPK2-related disorder

Similar variants

CMPK2 p.Arg9Ser Uncertain significance ★ ⚠ same condition
CMPK2 p.Cys76Tyr Uncertain significance ⚠ same condition
CMPK2 p.Pro159Leu Likely benign same condition
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

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-his357gln (accessed [today's date]).

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