Is CHST9 p.Pro359Leu (c.1076C>T) pathogenic?

CHST9 p.Pro359Leu (c.1076C>T) is classified Uncertain significance in CHST9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely pathogenic (0.8042); Very rare (popmax 0.00167%, amr).

How common is CHST9 p.Pro359Leu (c.1076C>T) in the general population?

CHST9 p.Pro359Leu (c.1076C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CHST9 p.Pro359Leu (c.1076C>T)?

AlphaMissense predicts likely pathogenic (score 0.8042) — an in-silico prediction, not a clinical call.

CHST9 p.Pro359Leu

c.1076C>T · rs1047731634 · VCV3144774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8042	likely pathogenic
REVEL	0.612	indeterminate
SaProt	LLR -14.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 227 kb · p 0.58 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,998 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,574 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
European (non-Finnish)	0.000593%	168,537

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.Pro359Leu
Coding: c.1076C>T
dbSNP: rs1047731634
Type: single nucleotide variant
Location: chr18:26916515 (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-pro359leu (accessed [today's date]).

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