Is CKM p.Ser147Ala (c.439T>G) pathogenic?

CKM p.Ser147Ala (c.439T>G) is classified Uncertain significance in CKM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: ambiguous (0.3707); Very rare (popmax 0.00401%, afr).

How common is CKM p.Ser147Ala (c.439T>G) in the general population?

CKM p.Ser147Ala (c.439T>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CKM p.Ser147Ala (c.439T>G)?

AlphaMissense predicts ambiguous (score 0.3707) — an in-silico prediction, not a clinical call.

CKM p.Ser147Ala

c.439T>G · VCV4229294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3707	ambiguous
REVEL	0.223	benign-leaning
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.25 · regional, not allelic
Overall
CADD	26.2	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 0.00401% African / African-American · 3/74,872 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00025% 4/1,600,318 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,957
Admixed American	0.00167%	59,960

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.Ser147Ala
Coding: c.439T>G
MANE Select: NM_001824
Type: single nucleotide variant
Location: chr19:45315507 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.92 · 2 PDB
Residue 147: the phosphagen kinase c-terminal domain

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-ser147ala (accessed [today's date]).

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