Is CHKB p.Lys27= (c.81G>A) pathogenic?

CHKB p.Lys27= (c.81G>A) is classified Likely benign in CHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-14). Very rare (popmax 0.00669%, afr); Associated with megaconial type congenital muscular dystrophy.

What condition is associated with CHKB p.Lys27= (c.81G>A)?

CHKB p.Lys27= (c.81G>A) is associated with megaconial type congenital muscular dystrophy (ClinVar).

How common is CHKB p.Lys27= (c.81G>A) in the general population?

CHKB p.Lys27= (c.81G>A) is very rare (popmax 0.00669%, afr) (gnomAD).

How is Megaconial congenital muscular dystrophy inherited?

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

CHKB p.Lys27=

c.81G>A · rs774227072 · VCV1634493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, afr)

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 0.42	GERP -0.4
Overall
CADD	8.895	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% African / African-American · 5/74,770 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000994% 16/1,609,894 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00669%	14,954
Remaining individualsnot grpmax-eligible	0.00161%	62,264
European (non-Finnish)	0.000848%	117,903

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.Lys27=
Coding: c.81G>A
MANE Select: NM_005198
dbSNP: rs774227072
Type: single nucleotide variant
Location: chr22:50582701 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 3 PDB

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.Lys27Arg Uncertain significance ★★ ⚠ same residue
CHKB p.Lys27Met Uncertain significance ★★ ⚠ same residue
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

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-lys27 (accessed [today's date]).

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