Is CHST3 p.Pro176Arg (c.527C>G) pathogenic?

CHST3 p.Pro176Arg (c.527C>G) is classified Uncertain significance in CHST3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.1039); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHST3 p.Pro176Arg (c.527C>G)?

CHST3 p.Pro176Arg (c.527C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHST3 p.Pro176Arg (c.527C>G) in the general population?

CHST3 p.Pro176Arg (c.527C>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CHST3 p.Pro176Arg (c.527C>G)?

AlphaMissense predicts likely benign (score 0.1039) — an in-silico prediction, not a clinical call.

CHST3 p.Pro176Arg

c.527C>G · VCV4228630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1039 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1039	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -7.41	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 2.3	GERP -0.53, phastCons 0.93
Regional constraint	o/e 1.03	unconstrained · MANE · 2,625 bp · p 0.38 · regional, not allelic
Overall
CADD	13.67	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 0.00446% East Asian · 2/44,868 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000311% 5/1,606,924 alleles · very rare exomes 4/1,454,598 · genomes 1/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,434
Remaining individualsnot grpmax-eligible	0.0016%	62,408
European (non-Finnish)	0.00017%	589,877

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: CHST3
Protein: p.Pro176Arg
Coding: c.527C>G
MANE Select: NM_004273
Type: single nucleotide variant
Location: chr10:72007558 (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.Pro176= Likely benign ★★ same residue
CHST3 p.Pro176Leu Uncertain significance ★ ⚠ 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

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-pro176arg (accessed [today's date]).

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