Is CHKA p.Cys6fs (c.14dup) pathogenic?

CHKA p.Cys6fs (c.14dup) is classified Likely pathogenic in CHKA (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-08). Absent from gnomAD; Associated with microcephaly.

What condition is associated with CHKA p.Cys6fs (c.14dup)?

CHKA p.Cys6fs (c.14dup) is associated with microcephaly, neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures (ClinVar).

How common is CHKA p.Cys6fs (c.14dup) in the general population?

CHKA p.Cys6fs (c.14dup) is absent from gnomAD (gnomAD).

CHKA p.Cys6fs

c.14dup · rs2153034844 · VCV1325847

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

microcephaly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.2	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHKA
Protein: p.Cys6fs
Coding: c.14dup
MANE Select: NM_001277
dbSNP: rs2153034844
Type: Duplication
Location: chr11:68121163 (GRCh38)
Gene constraint: LOEUF 0.926 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.95 · 26 PDB
Residue 6: the 'disordered' region

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

Disease context

microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures

Similar variants

CHKA p.Glu230Lys Uncertain significance ★★ ⚠ same condition
CHKA p.Arg141Trp Likely pathogenic ★ same condition
CHKA p.Phe341Leu Likely pathogenic ★ same condition
CHKA p.Pro194Ser Likely pathogenic ★ same condition
CHKA p.63LP[3] Uncertain significance ★ same condition
CHKA p.Arg204Leu Uncertain significance ★ ⚠ same condition
CHKA p.Met1Thr Uncertain significance ★ same condition
CHKA p.Pro64Gln 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/chka-p-cys6fs (accessed [today's date]).

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