Is CHKB p.Leu91Gln (c.272T>A) pathogenic?

CHKB p.Leu91Gln (c.272T>A) is classified Uncertain significance in CHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). AlphaMissense: likely benign (0.1344); Ultra-rare (popmax 0.0217%, mid); Associated with Inborn genetic diseases.

What condition is associated with CHKB p.Leu91Gln (c.272T>A)?

CHKB p.Leu91Gln (c.272T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CHKB p.Leu91Gln (c.272T>A) in the general population?

CHKB p.Leu91Gln (c.272T>A) is ultra-rare (popmax 0.0217%, mid) (gnomAD).

What do computational predictors say about CHKB p.Leu91Gln (c.272T>A)?

AlphaMissense predicts likely benign (score 0.1344) — an in-silico prediction, not a clinical call.

CHKB p.Leu91Gln

c.272T>A · rs757118700 · VCV2496024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1344	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -8.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 8.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,597 bp · p 0.53 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0217% Middle Eastern · 1/4,600 alleles

Filtering AF 0.00373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00264%

Overall 0.00104% 15/1,437,848 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0217%	4,600
South Asian	0.00803%	12,455
Remaining individualsnot grpmax-eligible	0.00163%	61,488
European (non-Finnish)	0.000512%	195,144

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: CHKB
Protein: p.Leu91Gln
Coding: c.272T>A
MANE Select: NM_005198
dbSNP: rs757118700
Type: single nucleotide variant
Location: chr22:50582310 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 3 PDB
Residue 91: a UniProt-annotated variant site (in mdcmc; loss of choline kinase activity; decreased amount of phosphatidylcholine in patients cells)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHKB p.Gln309Glu Uncertain significance ★★ ⚠ same condition
CHKB p.Glu97Asp Uncertain significance ★★ ⚠ same condition
CHKB p.Gly12Glu Uncertain significance ★★ ⚠ same condition
CHKB p.Gly190Glu Uncertain significance ★★ ⚠ same condition
CHKB p.Gly386Glu Uncertain significance ★★ ⚠ same condition
CHKB p.His315Arg Uncertain significance ★★ ⚠ same condition
CHKB p.Leu334Pro Uncertain significance ★★ ⚠ same condition
CHKB p.Leu371Met Uncertain significance ★★ ⚠ same condition

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/chkb-p-leu91gln (accessed [today's date]).

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