Is CMPK2 p.Arg234Gln (c.701G>A) pathogenic?

CMPK2 p.Arg234Gln (c.701G>A) is classified Likely benign in CMPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0605); Ultra-rare (popmax 0.0387%, afr).

How common is CMPK2 p.Arg234Gln (c.701G>A) in the general population?

CMPK2 p.Arg234Gln (c.701G>A) is ultra-rare (popmax 0.0387%, afr) (gnomAD).

What do computational predictors say about CMPK2 p.Arg234Gln (c.701G>A)?

AlphaMissense predicts likely benign (score 0.0605) — an in-silico prediction, not a clinical call.

CMPK2 p.Arg234Gln

c.701G>A · rs777709920 · VCV3146248

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0605 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0387%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	gain · loss 0.09 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -8	GERP -3.9
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic
Overall
CADD	0.588	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 0.0387% African / African-American · 29/74,916 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.00242% 39/1,613,954 alleles · ultra-rare exomes 24/1,461,822 · genomes 15/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0387%	2,583
South Asian	0.00549%	18,214
Remaining individualsnot grpmax-eligible	0.0032%	31,241
Admixed American	0.00167%	59,996
European (non-Finnish)	0.000169%	589,995

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.Arg234Gln
Coding: c.701G>A
MANE Select: NM_207315
dbSNP: rs777709920
Type: single nucleotide variant
Location: chr2:6863553 (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-arg234gln (accessed [today's date]).

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