Is CHST3 p.Lys267Gln (c.799A>C) pathogenic?

CHST3 p.Lys267Gln (c.799A>C) is classified Uncertain significance in CHST3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: ambiguous (0.4793); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHST3 p.Lys267Gln (c.799A>C)?

CHST3 p.Lys267Gln (c.799A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHST3 p.Lys267Gln (c.799A>C) in the general population?

CHST3 p.Lys267Gln (c.799A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CHST3 p.Lys267Gln (c.799A>C)?

AlphaMissense predicts ambiguous (score 0.4793) — an in-silico prediction, not a clinical call.

CHST3 p.Lys267Gln

c.799A>C · VCV4228632

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4793	ambiguous
REVEL	0.565	indeterminate
SaProt	LLR -6.70	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP -0.46, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,625 bp · p 0.38 · regional, not allelic
Overall
CADD	26.3	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 0.00167% Admixed American · 1/59,912 alleles

Overall 0.00131% 2/152,164 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,912
Remaining individualsnot grpmax-eligible	0.00161%	62,264

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: CHST3
Protein: p.Lys267Gln
Coding: c.799A>C
MANE Select: NM_004273
Type: single nucleotide variant
Location: chr10:72007830 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.58

Full CHST3 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

Similar variants

CHST3 p.Lys267Arg Uncertain significance ★ ⚠ same residue
CHST3 p.Ala182Thr Uncertain significance ★★ ⚠ same condition
CHST3 p.Ala389Thr Uncertain significance ★★ ⚠ same condition
CHST3 p.Ala68Thr Uncertain significance ★★ ⚠ same condition
CHST3 p.Ile348Leu Uncertain significance ★★ ⚠ same condition
CHST3 p.Leu90Phe Uncertain significance ★★ ⚠ same condition
CHST3 p.Leu90Pro Uncertain significance ★★ ⚠ same condition
CHST3 p.Pro285Ser 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/chst3-p-lys267gln (accessed [today's date]).

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