Is CHST9 p.Trp151Arg (c.451T>C) pathogenic?

CHST9 p.Trp151Arg (c.451T>C) is classified Uncertain significance in CHST9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.2116); Ultra-rare (popmax 0.0334%, eas).

How common is CHST9 p.Trp151Arg (c.451T>C) in the general population?

CHST9 p.Trp151Arg (c.451T>C) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about CHST9 p.Trp151Arg (c.451T>C)?

AlphaMissense predicts likely benign (score 0.2116) — an in-silico prediction, not a clinical call.

CHST9 p.Trp151Arg

c.451T>C · rs374131760 · VCV2551751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2116 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2116	likely benign
REVEL	0.38	indeterminate
SaProt	LLR -4.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 227 kb · p 0.58 · regional, not allelic
Overall
CADD	19.43	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 0.0334% East Asian · 15/44,878 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00167% 27/1,613,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
Remaining individualsnot grpmax-eligible	0.0176%	5,680
European (non-Finnish)	8.48e-05%	1,179,871

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: CHST9
Protein: p.Trp151Arg
Coding: c.451T>C
dbSNP: rs374131760
Type: single nucleotide variant
Location: chr18:26917140 (GRCh38)

Full CHST9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/chst9-p-trp151arg (accessed [today's date]).

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