Is CHST6 p.Ala332Asp (c.995C>A) pathogenic?

CHST6 p.Ala332Asp (c.995C>A) is classified Uncertain significance in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: ambiguous (0.468); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHST6 p.Ala332Asp (c.995C>A)?

CHST6 p.Ala332Asp (c.995C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CHST6 p.Ala332Asp (c.995C>A) in the general population?

CHST6 p.Ala332Asp (c.995C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHST6 p.Ala332Asp (c.995C>A)?

AlphaMissense predicts ambiguous (score 0.468) — an in-silico prediction, not a clinical call.

CHST6 p.Ala332Asp

c.995C>A · VCV4228660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.468 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.468	ambiguous
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -7.48	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHST6
Protein: p.Ala332Asp
Coding: c.995C>A
MANE Select: NM_021615
Type: single nucleotide variant
Location: chr16:75478834 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66

Full CHST6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHST6 p.Ala286Val Uncertain significance ★★ ⚠ same condition
CHST6 p.Ala352Val Uncertain significance ★★ ⚠ same condition
CHST6 p.Arg240Ser Uncertain significance ★★ ⚠ same condition
CHST6 p.Arg267Cys Uncertain significance ★★ ⚠ same condition
CHST6 p.Arg344Cys Uncertain significance ★★ ⚠ same condition
CHST6 p.Gln82Pro Uncertain significance ★★ ⚠ same condition
CHST6 p.Glu317Gln Uncertain significance ★★ ⚠ same condition
CHST6 p.Gly238Asp Uncertain significance ★★ ⚠ same condition

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/chst6-p-ala332asp (accessed [today's date]).

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