Is CHKB p.Ile148= (c.444C>A) pathogenic?

CHKB p.Ile148= (c.444C>A) is classified Likely benign in CHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). Absent from gnomAD v4.1; Associated with megaconial type congenital muscular dystrophy.

What condition is associated with CHKB p.Ile148= (c.444C>A)?

CHKB p.Ile148= (c.444C>A) is associated with megaconial type congenital muscular dystrophy (ClinVar).

How common is CHKB p.Ile148= (c.444C>A) in the general population?

CHKB p.Ile148= (c.444C>A) is absent from gnomAD v4.1 (gnomAD).

How is Megaconial congenital muscular dystrophy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CHKB p.Ile148=

c.444C>A · rs917349763 · VCV2711681

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

megaconial type congenital muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.47	donor gain · deltas
Constraint at this position
Conservation	phyloP 4.2	GERP 2.4, phastCons 1
Overall
CADD	18.69	PHRED · no single calibrated threshold — expert panels disagree

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.Ile148=
Coding: c.444C>A
MANE Select: NM_005198
dbSNP: rs917349763
Type: single nucleotide variant
Location: chr22:50581752 (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 148: a UniProt-annotated variant site (in mdcmc; loss of choline kinase activity; decreased amount of phosphatidylcholine in patients cells); a binding site

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

Disease context

megaconial type congenital muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Megaconial congenital muscular dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CHKB p.Gln51Ter Pathogenic/Likely pathogenic ★★ same condition
CHKB c.*208T>G Uncertain significance ★★ same condition
CHKB p.Ala361Val Uncertain significance ★★ ⚠ same condition
CHKB p.Arg344Trp Uncertain significance ★★ ⚠ same condition
CHKB p.Arg62Cys Uncertain significance ★★ ⚠ same condition
CHKB p.Gln309Glu Uncertain significance ★★ ⚠ same condition
CHKB p.Glu214Asp Uncertain significance ★★ ⚠ same condition
CHKB p.Glu336Lys 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-ile148 (accessed [today's date]).

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