Is CHST2 p.Ala116Pro (c.346G>C) pathogenic?

CHST2 p.Ala116Pro (c.346G>C) is classified Uncertain significance in CHST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0568); Ultra-rare (popmax 0.0342%, afr).

How common is CHST2 p.Ala116Pro (c.346G>C) in the general population?

CHST2 p.Ala116Pro (c.346G>C) is ultra-rare (popmax 0.0342%, afr) (gnomAD).

What do computational predictors say about CHST2 p.Ala116Pro (c.346G>C)?

AlphaMissense predicts likely benign (score 0.0568) — an in-silico prediction, not a clinical call.

CHST2 p.Ala116Pro

c.346G>C · VCV4228608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0568 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0568	likely benign
REVEL	0.575	indeterminate
SaProt	LLR -5.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	phastCons 0.001
Regional constraint	o/e 1.18	unconstrained · MANE · 481 bp · p 0.0045 · regional, not allelic
Overall
CADD	9.871	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 0.0342% African / African-American · 24/70,152 alleles

Filtering AF 0.0236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0201%

Overall 0.00275% 41/1,491,858 alleles · ultra-rare exomes 31/1,339,600 · genomes 10/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0342%	2,923
Remaining individualsnot grpmax-eligible	0.0225%	4,443
South Asian	0.00269%	37,214
European (non-Finnish)	0.000177%	565,301

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.Ala116Pro
Coding: c.346G>C
MANE Select: NM_004267
Type: single nucleotide variant
Location: chr3:143121162 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.61
Residue 116: the 'disordered' region

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

Similar variants

CHST2 p.Ala116Ser Uncertain significance ★ ⚠ same residue
CHST2 p.Ala118Gly Uncertain significance ★ ⚠ same type
CHST2 p.Ala131Val Uncertain significance ★ ⚠ same type
CHST2 p.Ala24Val Uncertain significance ★ ⚠ same type
CHST2 p.Ala25Thr 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-ala116pro (accessed [today's date]).

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