Is CKM p.Val336Ala (c.1007T>C) pathogenic?

CKM p.Val336Ala (c.1007T>C) is classified Uncertain significance in CKM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely pathogenic (0.9727); Very rare (popmax 0.000254%, nfe).

How common is CKM p.Val336Ala (c.1007T>C) in the general population?

CKM p.Val336Ala (c.1007T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CKM p.Val336Ala (c.1007T>C)?

AlphaMissense predicts likely pathogenic (score 0.9727) — an in-silico prediction, not a clinical call.

CKM p.Val336Ala

c.1007T>C · rs1971057465 · VCV2480284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9727	likely pathogenic
REVEL	0.387	indeterminate
SaProt	LLR -14.36	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.25 · regional, not allelic
Overall
CADD	30.0	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 0.000254% European (non-Finnish) · 3/1,180,038 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,054 alleles · very rare

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.Val336Ala
Coding: c.1007T>C
MANE Select: NM_001824
dbSNP: rs1971057465
Type: single nucleotide variant
Location: chr19:45306889 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.92 · 2 PDB
Residue 336: the phosphagen kinase c-terminal domain; a β-strand

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-val336ala (accessed [today's date]).

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