Is CHST9 p.Ala407Val (c.1220C>T) pathogenic?

CHST9 p.Ala407Val (c.1220C>T) is classified Uncertain significance in CHST9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.086); Very rare (popmax 0.005%, amr).

How common is CHST9 p.Ala407Val (c.1220C>T) in the general population?

CHST9 p.Ala407Val (c.1220C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CHST9 p.Ala407Val (c.1220C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

CHST9 p.Ala407Val

c.1220C>T · VCV4228681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.5	GERP -0.092, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 227 kb · p 0.58 · regional, not allelic
Overall
CADD	15.5	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 0.005% Admixed American · 3/59,988 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000479% 7/1,461,490 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,996
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.000254%	393,230

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.Ala407Val
Coding: c.1220C>T
Type: single nucleotide variant
Location: chr18:26916371 (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-ala407val (accessed [today's date]).

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