Is CMPK2 p.His201Gln (c.603C>G) pathogenic?

CMPK2 p.His201Gln (c.603C>G) is classified Uncertain significance in CMPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely pathogenic (0.8958); Very rare (popmax 0.0013%, sas).

How common is CMPK2 p.His201Gln (c.603C>G) in the general population?

CMPK2 p.His201Gln (c.603C>G) is very rare (popmax 0.0013%, sas) (gnomAD).

What do computational predictors say about CMPK2 p.His201Gln (c.603C>G)?

AlphaMissense predicts likely pathogenic (score 0.8958) — an in-silico prediction, not a clinical call.

CMPK2 p.His201Gln

c.603C>G · VCV3494136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0013%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8958	likely pathogenic · top 10% in CMPK2
REVEL	0.194	benign-leaning
SaProt	LLR -5.49	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 2.1	GERP 0.69, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic
Overall
CADD	21.8	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 0.0013% South Asian · 1/76,734 alleles

Overall 0.000223% 3/1,344,202 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00173%	57,670
South Asiangrpmax	0.0013%	76,734
European (non-Finnish)	8.91e-05%	1,122,638

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His201Gln
Coding: c.603C>G
MANE Select: NM_207315
Type: single nucleotide variant
Location: chr2:6865094 (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-his201gln (accessed [today's date]).

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