Is CHST15 p.Pro198Ser (c.592C>T) pathogenic?

CHST15 p.Pro198Ser (c.592C>T) is classified Uncertain significance in CHST15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely pathogenic (0.5822); Ultra-rare (popmax 0.0184%, mid).

How common is CHST15 p.Pro198Ser (c.592C>T) in the general population?

CHST15 p.Pro198Ser (c.592C>T) is ultra-rare (popmax 0.0184%, mid) (gnomAD).

What do computational predictors say about CHST15 p.Pro198Ser (c.592C>T)?

AlphaMissense predicts likely pathogenic (score 0.5822) — an in-silico prediction, not a clinical call.

CHST15 p.Pro198Ser

c.592C>T · VCV3833260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5822	likely pathogenic
REVEL	0.731	pathogenic-leaning
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 1,346 bp · p 4.5e-05 · regional, not allelic
Overall
CADD	27.6	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 0.0184% Middle Eastern · 1/5,440 alleles

Filtering AF 0.00777% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00589%

Overall 0.00114% 15/1,313,772 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0184%	5,440
South Asian	0.0144%	6,937
Remaining individualsnot grpmax-eligible	0.00358%	27,902
European (non-Finnish)	0.000181%	553,266

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: CHST15
Protein: p.Pro198Ser
Coding: c.592C>T
MANE Select: NM_001270764
Type: single nucleotide variant
Location: chr10:124044874 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.20

Full CHST15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST15 p.Ala16Thr Benign ★★ same type
CHST15 p.Arg224= Benign ★★ same type
CHST15 p.Ala241Val Uncertain significance ★ ⚠ same type
CHST15 p.Ala283Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala321Thr Uncertain significance ★ ⚠ same type
CHST15 p.Ala330Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala357Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala412Thr 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/chst15-p-pro198ser (accessed [today's date]).

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