Is CHKB p.Ala13Val (c.38C>T) pathogenic?

CHKB p.Ala13Val (c.38C>T) is classified Conflicting classifications of pathogenicity in CHKB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.0984); Rare (popmax 0.154%, sas); Associated with Inborn genetic diseases.

What condition is associated with CHKB p.Ala13Val (c.38C>T)?

CHKB p.Ala13Val (c.38C>T) is associated with Inborn genetic diseases, megaconial type congenital muscular dystrophy (ClinVar).

How common is CHKB p.Ala13Val (c.38C>T) in the general population?

CHKB p.Ala13Val (c.38C>T) is rare (popmax 0.154%, sas) (gnomAD).

What do computational predictors say about CHKB p.Ala13Val (c.38C>T)?

AlphaMissense predicts likely benign (score 0.0984) — an in-silico prediction, not a clinical call.

CHKB p.Ala13Val

c.38C>T · rs779585255 · VCV388744

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0984 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0984	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.31	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 0.38	GERP 1.8
Regional constraint	o/e 1.03	unconstrained · MANE · 3,597 bp · p 0.53 · regional, not allelic
Overall
CADD	17.56	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 0.154% South Asian · 137/89,224 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.0484% 773/1,597,228 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.154%	651
European (non-Finnish)	0.0517%	1,936
Remaining individualsnot grpmax-eligible	0.0308%	3,250
Middle Eastern	0.0168%	5,944
African / African-American	0.00672%	14,884
Finnishnot grpmax-eligible	0.00662%	15,107
East Asian	0.00227%	43,980

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.Ala13Val
Coding: c.38C>T
MANE Select: NM_005198
dbSNP: rs779585255
Type: single nucleotide variant
Location: chr22:50582744 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: megaconial type congenital muscular dystrophy

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-ala13val (accessed [today's date]).

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