Is CHKA p.Pro64Gln (c.191C>A) pathogenic?

CHKA p.Pro64Gln (c.191C>A) is classified Uncertain significance in CHKA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). AlphaMissense: likely benign (0.106); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures.

How common is CHKA p.Pro64Gln (c.191C>A) in the general population?

CHKA p.Pro64Gln (c.191C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHKA p.Pro64Gln (c.191C>A)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

CHKA p.Pro64Gln

Q: What condition is associated with CHKA p.Pro64Gln (c.191C>A)?

CHKA p.Pro64Gln (c.191C>A) is associated with neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures (ClinVar).

c.191C>A · VCV3341486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,119,906)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.49, phastCons 0.93
Regional constraint	o/e 1.00	unconstrained · MANE · 67 kb · p 0.94 · regional, not allelic
Overall
CADD	19.42	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

No allele count reported in gnomAD v4.1 (AN 1,119,906). 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.Pro64Gln
Coding: c.191C>A
MANE Select: NM_001277
Type: single nucleotide variant
Location: chr11:68120987 (GRCh38)
Gene constraint: LOEUF 0.926 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.95 · 26 PDB
Residue 64: the 'disordered' region

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

Disease context

neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHKA p.Pro64Ser Uncertain significance ★ ⚠ same residue
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.Arg204Leu Uncertain significance ★ ⚠ same condition
CHKA p.Met1Thr Uncertain significance ★ same condition
CHKA p.Cys6fs Likely pathogenic ★ 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-pro64gln (accessed [today's date]).

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