Is CHST3 p.Pro378Arg (c.1133C>G) pathogenic?

CHST3 p.Pro378Arg (c.1133C>G) is classified Uncertain significance in CHST3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely pathogenic (0.8815); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHST3 p.Pro378Arg (c.1133C>G)?

CHST3 p.Pro378Arg (c.1133C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHST3 p.Pro378Arg (c.1133C>G) in the general population?

CHST3 p.Pro378Arg (c.1133C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHST3 p.Pro378Arg (c.1133C>G)?

AlphaMissense predicts likely pathogenic (score 0.8815) — an in-silico prediction, not a clinical call.

CHST3 p.Pro378Arg

c.1133C>G · VCV3492728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8815 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8815	likely pathogenic
REVEL	0.921	moderately pathogenic-leaning
SaProt	LLR -13.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,625 bp · p 0.38 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHST3
Protein: p.Pro378Arg
Coding: c.1133C>G
MANE Select: NM_004273
Type: single nucleotide variant
Location: chr10:72008164 (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.Pro378= Likely benign ★ 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-pro378arg (accessed [today's date]).

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