Is CKM p.Pro91Ser (c.271C>T) pathogenic?

CKM p.Pro91Ser (c.271C>T) is classified Uncertain significance in CKM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-09). AlphaMissense: likely benign (0.3145); Very rare (popmax 0.00501%, amr).

How common is CKM p.Pro91Ser (c.271C>T) in the general population?

CKM p.Pro91Ser (c.271C>T) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about CKM p.Pro91Ser (c.271C>T)?

AlphaMissense predicts likely benign (score 0.3145) — an in-silico prediction, not a clinical call.

CKM p.Pro91Ser

c.271C>T · rs765177605 · VCV2688787

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3145 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3145	likely benign
REVEL	0.697	pathogenic-leaning
SaProt	LLR -12.91	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.25 · regional, not allelic
Overall
CADD	24.1	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 0.00501% Admixed American · 3/59,928 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00143% 23/1,613,780 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,976
Remaining individualsnot grpmax-eligible	0.0032%	31,242
Finnishnot grpmax-eligible	0.00156%	64,010
European (non-Finnish)	0.00136%	73,746
African / African-American	0.00134%	74,858

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.Pro91Ser
Coding: c.271C>T
MANE Select: NM_001824
dbSNP: rs765177605
Type: single nucleotide variant
Location: chr19:45317902 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.92 · 2 PDB
Residue 91: the phosphagen kinase n-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.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
CKM p.Arg148Cys 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-pro91ser (accessed [today's date]).

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