Is CKM p.Arg152Gln (c.455G>A) pathogenic?

CKM p.Arg152Gln (c.455G>A) is classified Uncertain significance in CKM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely pathogenic (0.6967); Very rare (popmax 0.00333%, amr).

How common is CKM p.Arg152Gln (c.455G>A) in the general population?

CKM p.Arg152Gln (c.455G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CKM p.Arg152Gln (c.455G>A)?

AlphaMissense predicts likely pathogenic (score 0.6967) — an in-silico prediction, not a clinical call.

CKM p.Arg152Gln

c.455G>A · rs146705516 · VCV2600838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6967	likely pathogenic
REVEL	0.302	indeterminate
SaProt	LLR -11.21	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.25 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00333% Admixed American · 2/59,974 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00269% 43/1,599,596 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00801%	12,477
Admixed Americangrpmax	0.00333%	29,987
South Asian	0.0033%	30,335
European (non-Finnish)	0.00271%	36,867
East Asian	0.00223%	44,864

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: CKM
Protein: p.Arg152Gln
Coding: c.455G>A
MANE Select: NM_001824
dbSNP: rs146705516
Type: single nucleotide variant
Location: chr19:45315491 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.92 · 2 PDB
Residue 152: the phosphagen kinase c-terminal domain; an α-helix

Full CKM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKM p.Leu127Val Uncertain significance ★★ ⚠ same type
CKM p.Pro91Ser Uncertain significance ★★ ⚠ same type
CKM p.Arg251Pro Likely benign ★★ ⚠ same type
CKM p.Ala214Thr Uncertain significance ★ ⚠ same type
CKM p.Ala267Asp Uncertain significance ★ ⚠ same type
CKM p.Ala267Val Uncertain significance ★ ⚠ same type
CKM p.Arg135Gly Uncertain significance ★ ⚠ same type
CKM p.Arg135His 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/ckm-p-arg152gln (accessed [today's date]).

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