Is CHST1 p.Arg198Ser (c.592C>A) pathogenic?

CHST1 p.Arg198Ser (c.592C>A) is classified Uncertain significance in CHST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: likely benign (0.3354); Very rare (popmax 0.00989%, sas).

How common is CHST1 p.Arg198Ser (c.592C>A) in the general population?

CHST1 p.Arg198Ser (c.592C>A) is very rare (popmax 0.00989%, sas) (gnomAD).

What do computational predictors say about CHST1 p.Arg198Ser (c.592C>A)?

AlphaMissense predicts likely benign (score 0.3354) — an in-silico prediction, not a clinical call.

CHST1 p.Arg198Ser

c.592C>A · rs747837712 · VCV2260081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3354 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3354	likely benign
REVEL	0.512	indeterminate
SaProt	LLR -6.90	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 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,232 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	22.7	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 0.00989% South Asian · 9/91,036 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.00112% 18/1,603,360 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,115
East Asian	0.00891%	11,218
Admixed American	0.00333%	29,986
Remaining individualsnot grpmax-eligible	0.0016%	62,382
European (non-Finnish)	0.00017%	589,859

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.Arg198Ser
Coding: c.592C>A
MANE Select: NM_003654
dbSNP: rs747837712
Type: single nucleotide variant
Location: chr11:45650332 (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

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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-arg198ser (accessed [today's date]).

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