Is CHST1 p.Pro102Ser (c.304C>T) pathogenic?

CHST1 p.Pro102Ser (c.304C>T) is classified Uncertain significance in CHST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). AlphaMissense: likely benign (0.1458); Ultra-rare (popmax 0.0483%, amr).

How common is CHST1 p.Pro102Ser (c.304C>T) in the general population?

CHST1 p.Pro102Ser (c.304C>T) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

What do computational predictors say about CHST1 p.Pro102Ser (c.304C>T)?

AlphaMissense predicts likely benign (score 0.1458) — an in-silico prediction, not a clinical call.

CHST1 p.Pro102Ser

c.304C>T · VCV3267200

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1458 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1458	likely benign
REVEL	0.56	indeterminate
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.59, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,232 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	24.9	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 0.0483% Admixed American · 29/60,032 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0298%

Overall 0.00223% 36/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0064%	15,626
African / African-American	0.00133%	75,074
European (non-Finnish)	0.000169%	589,995

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: CHST1
Protein: p.Pro102Ser
Coding: c.304C>T
MANE Select: NM_003654
Type: single nucleotide variant
Location: chr11:45650620 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 87.90

Full CHST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST1 p.Arg59His Uncertain significance ★★ ⚠ same type
CHST1 p.Ala12Thr Uncertain significance ★ ⚠ same type
CHST1 p.Ala388Thr Uncertain significance ★ ⚠ same type
CHST1 p.Ala43Val Uncertain significance ★ ⚠ same type
CHST1 p.Ala54Thr Uncertain significance ★ ⚠ same type
CHST1 p.Arg114Gln Uncertain significance ★ ⚠ same type
CHST1 p.Arg198Ser Uncertain significance ★ ⚠ same type
CHST1 p.Arg217His 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/chst1-p-pro102ser (accessed [today's date]).

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