Is CHST2 p.Pro361Arg (c.1082C>G) pathogenic?

CHST2 p.Pro361Arg (c.1082C>G) is classified Uncertain significance in CHST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). AlphaMissense: ambiguous (0.4126); Very rare (popmax 8.62e-05%, nfe).

How common is CHST2 p.Pro361Arg (c.1082C>G) in the general population?

CHST2 p.Pro361Arg (c.1082C>G) is very rare (popmax 8.62e-05%, nfe) (gnomAD).

What do computational predictors say about CHST2 p.Pro361Arg (c.1082C>G)?

AlphaMissense predicts ambiguous (score 0.4126) — an in-silico prediction, not a clinical call.

CHST2 p.Pro361Arg

c.1082C>G · rs533372458 · VCV2257993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4126 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.62e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4126	ambiguous
REVEL	0.63	indeterminate
SaProt	LLR -7.51	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 509 bp · p 0.8 · regional, not allelic
Overall
CADD	25.8	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 8.62e-05% European (non-Finnish) · 1/1,159,452 alleles

Overall 7.02e-05% 1/1,424,500 alleles · very rare

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.Pro361Arg
Coding: c.1082C>G
MANE Select: NM_004267
dbSNP: rs533372458
Type: single nucleotide variant
Location: chr3:143121898 (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-pro361arg (accessed [today's date]).

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