Is CHKB p.Phe83= (c.249C>T) pathogenic?

CHKB p.Phe83= (c.249C>T) is classified Benign/Likely benign in CHKB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Rare (popmax 0.398%, nfe); Associated with megaconial type congenital muscular dystrophy.

What condition is associated with CHKB p.Phe83= (c.249C>T)?

CHKB p.Phe83= (c.249C>T) is associated with megaconial type congenital muscular dystrophy (ClinVar).

How common is CHKB p.Phe83= (c.249C>T) in the general population?

CHKB p.Phe83= (c.249C>T) is rare (popmax 0.398%, nfe) (gnomAD).

How is Megaconial congenital muscular dystrophy inherited?

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

CHKB p.Phe83=

c.249C>T · rs180979987 · VCV342176

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.398%, nfe)

Conditions

megaconial type congenital muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.2, phastCons 1
Overall
CADD	14.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.398% European (non-Finnish) · 4,627/1,162,420 alleles

Filtering AF 0.388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.385%

Overall 0.307% 4,825/1,574,022 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.398%	251
Remaining individualsnot grpmax-eligible	0.164%	609
Ashkenazi Jewishnot grpmax-eligible	0.118%	848
Finnishnot grpmax-eligible	0.0442%	2,262
African / African-American	0.039%	2,563
Admixed American	0.0147%	6,780
South Asian	0.00116%	85,838

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.Phe83=
Coding: c.249C>T
MANE Select: NM_005198
dbSNP: rs180979987
Type: single nucleotide variant
Location: chr22:50582333 (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 83: a UniProt-annotated variant site (in mdcmc; loss of choline kinase activity; decreased amount of phosphatidylcholine in patients cells); a β-strand

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-phe83 (accessed [today's date]).

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