Is CHKB p.Arg344Trp (c.1030C>T) pathogenic?

CHKB p.Arg344Trp (c.1030C>T) is classified Uncertain significance in CHKB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-16). AlphaMissense: likely benign (0.2728); Ultra-rare (popmax 0.0329%, mid); Associated with megaconial type congenital muscular dystrophy.

What condition is associated with CHKB p.Arg344Trp (c.1030C>T)?

CHKB p.Arg344Trp (c.1030C>T) is associated with megaconial type congenital muscular dystrophy (ClinVar).

How common is CHKB p.Arg344Trp (c.1030C>T) in the general population?

CHKB p.Arg344Trp (c.1030C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Megaconial congenital muscular dystrophy inherited?

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

What do computational predictors say about CHKB p.Arg344Trp (c.1030C>T)?

AlphaMissense predicts likely benign (score 0.2728) — an in-silico prediction, not a clinical call.

CHKB p.Arg344Trp

c.1030C>T · rs138074497 · VCV1723094

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

megaconial type congenital muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.2728	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -11.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Pangolin	Δ0.24	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.26	GERP -1.4, phastCons 0.004
Regional constraint	o/e 1.03	unconstrained · MANE · 3,597 bp · p 0.53 · regional, not allelic
Overall
CADD	22.2	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 0.0329% Middle Eastern · 2/6,072 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.0018% 29/1,607,706 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,036
Admixed American	0.01%	9,989
African / African-American	0.00536%	18,650
South Asian	0.0033%	30,299
Remaining individualsnot grpmax-eligible	0.00161%	62,294
European (non-Finnish)	0.00111%	90,373

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.Arg344Trp
Coding: c.1030C>T
MANE Select: NM_005198
dbSNP: rs138074497
Type: single nucleotide variant
Location: chr22:50579728 (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 344: 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

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.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
CHKB p.Glu97Asp 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-arg344trp (accessed [today's date]).

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