Is CHST2 p.Ala25Thr (c.73G>A) pathogenic?

CHST2 p.Ala25Thr (c.73G>A) is classified Uncertain significance in CHST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1329); Ultra-rare (popmax 0.0132%, amr).

How common is CHST2 p.Ala25Thr (c.73G>A) in the general population?

CHST2 p.Ala25Thr (c.73G>A) is ultra-rare (popmax 0.0132%, amr) (gnomAD).

What do computational predictors say about CHST2 p.Ala25Thr (c.73G>A)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

CHST2 p.Ala25Thr

c.73G>A · VCV4228607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -8.21	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 1.6	phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 481 bp · p 0.0045 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% Admixed American · 5/38,016 alleles

Filtering AF 0.00508% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00328%

Overall 0.000819% 12/1,465,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0132%	7,603
African / African-American	0.00741%	13,489
Remaining individualsnot grpmax-eligible	0.00357%	27,991

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: CHST2
Protein: p.Ala25Thr
Coding: c.73G>A
MANE Select: NM_004267
Type: single nucleotide variant
Location: chr3:143120889 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.61

Full CHST2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST2 p.Ala116Pro Uncertain significance ★ ⚠ same type
CHST2 p.Ala116Ser Uncertain significance ★ ⚠ same type
CHST2 p.Ala118Gly Uncertain significance ★ ⚠ same type
CHST2 p.Ala131Val Uncertain significance ★ ⚠ same type
CHST2 p.Ala24Val Uncertain significance ★ ⚠ same type
CHST2 p.Ala387Gly Uncertain significance ★ ⚠ same type
CHST2 p.Ala455Val Uncertain significance ★ ⚠ same type
CHST2 p.Ala476Thr 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/chst2-p-ala25thr (accessed [today's date]).

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