Is CHKA p.Ala102= (c.306C>T) pathogenic?

CHKA p.Ala102= (c.306C>T) is classified Likely benign in CHKA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Very rare (popmax 0.00375%, nfe).

How common is CHKA p.Ala102= (c.306C>T) in the general population?

CHKA p.Ala102= (c.306C>T) is very rare (popmax 0.00375%, nfe) (gnomAD).

CHKA p.Ala102=

c.306C>T · VCV4681640

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00375%, nfe)

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 4.9	GERP -0.94, phastCons 1
Overall
CADD	13.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00375% European (non-Finnish) · 39/1,040,950 alleles

Filtering AF 0.0028% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00302% 41/1,357,200 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00375%	26,691
Remaining individualsnot grpmax-eligible	0.00209%	47,806
South Asian	0.00148%	67,688

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: CHKA
Protein: p.Ala102=
Coding: c.306C>T
MANE Select: NM_001277
Type: single nucleotide variant
Location: chr11:68120872 (GRCh38)
Gene constraint: LOEUF 0.926 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.95 · 26 PDB
Residue 102: an α-helix

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

Similar variants

CHKA p.Glu230Lys Uncertain significance ★★ ⚠ same type
CHKA p.Arg141Trp Likely pathogenic ★ same type
CHKA p.Gly344Ter Likely pathogenic ★ same type
CHKA p.Phe341Leu Likely pathogenic ★ ⚠ same type
CHKA p.Pro194Ser Likely pathogenic ★ same type
CHKA p.Ala188Thr Uncertain significance ★ ⚠ same type
CHKA p.Ala27Thr Uncertain significance ★ ⚠ same type
CHKA p.Ala385Thr Uncertain significance ★ ⚠ same type

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-ala102 (accessed [today's date]).

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