Is CMPK2 p.Cys117Ser (c.350G>C) pathogenic?

CMPK2 p.Cys117Ser (c.350G>C) is classified Uncertain significance in CMPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely benign (0.1091); Very rare (popmax 0.00229%, amr).

How common is CMPK2 p.Cys117Ser (c.350G>C) in the general population?

CMPK2 p.Cys117Ser (c.350G>C) is very rare (popmax 0.00229%, amr) (gnomAD).

What do computational predictors say about CMPK2 p.Cys117Ser (c.350G>C)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

CMPK2 p.Cys117Ser

c.350G>C · VCV3494128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -3.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.69, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic
Overall
CADD	15.61	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% Admixed American · 1/43,610 alleles

Overall 0.00131% 2/152,130 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00229%	43,610
European (non-Finnish)	8.92e-05%	1,121,700

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.Cys117Ser
Coding: c.350G>C
MANE Select: NM_207315
Type: single nucleotide variant
Location: chr2:6865347 (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-cys117ser (accessed [today's date]).

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