Is CHST2 p.Arg296Cys (c.886C>T) pathogenic?

CHST2 p.Arg296Cys (c.886C>T) is classified Uncertain significance in CHST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: ambiguous (0.4004); Very rare (popmax 0.00356%, amr).

How common is CHST2 p.Arg296Cys (c.886C>T) in the general population?

CHST2 p.Arg296Cys (c.886C>T) is very rare (popmax 0.00356%, amr) (gnomAD).

What do computational predictors say about CHST2 p.Arg296Cys (c.886C>T)?

AlphaMissense predicts ambiguous (score 0.4004) — an in-silico prediction, not a clinical call.

CHST2 p.Arg296Cys

c.886C>T · VCV4002755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4004 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4004	ambiguous
REVEL	0.713	pathogenic-leaning
SaProt	LLR -13.12	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 418 bp · p 0.0018 · regional, not allelic
Overall
CADD	31.0	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 0.00356% Admixed American · 2/56,194 alleles

Filtering AF 0.00059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000221%

Overall 0.000253% 4/1,582,680 alleles · very rare exomes 0/1,430,446 · genomes 4/152,234 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00356%	28,097
African / African-American	0.00134%	74,424
European (non-Finnish)	8.61e-05%	1,161,142

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.Arg296Cys
Coding: c.886C>T
MANE Select: NM_004267
Type: single nucleotide variant
Location: chr3:143121702 (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.Ala25Thr Uncertain significance ★ ⚠ same type
CHST2 p.Ala387Gly Uncertain significance ★ ⚠ same type
CHST2 p.Ala455Val 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-arg296cys (accessed [today's date]).

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