Is CHKB p.Asn224Ser (c.671A>G) pathogenic?

CHKB p.Asn224Ser (c.671A>G) is classified Uncertain significance in CHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely benign (0.0601); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHKB p.Asn224Ser (c.671A>G)?

CHKB p.Asn224Ser (c.671A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHKB p.Asn224Ser (c.671A>G) in the general population?

CHKB p.Asn224Ser (c.671A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHKB p.Asn224Ser (c.671A>G)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

CHKB p.Asn224Ser

c.671A>G · VCV3833027

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4.7
Regional constraint	o/e 1.03	unconstrained · MANE · 3,597 bp · p 0.53 · regional, not allelic
Overall
CADD	3.172	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHKB
Protein: p.Asn224Ser
Coding: c.671A>G
MANE Select: NM_005198
Type: single nucleotide variant
Location: chr22:50580571 (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 224: a UniProt-annotated variant site (in mdcmc; loss of choline kinase activity; decreased amount of phosphatidylcholine in patients cells); a UniProt-annotated variant site (in mdcmc); an α-helix

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.Asn224His Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-asn224ser (accessed [today's date]).

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