Is CHST6 p.Arg278Pro (c.833G>C) pathogenic?

CHST6 p.Arg278Pro (c.833G>C) is classified Uncertain significance in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.6846); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHST6 p.Arg278Pro (c.833G>C)?

CHST6 p.Arg278Pro (c.833G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHST6 p.Arg278Pro (c.833G>C) in the general population?

CHST6 p.Arg278Pro (c.833G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CHST6 p.Arg278Pro (c.833G>C)?

AlphaMissense predicts likely pathogenic (score 0.6846) — an in-silico prediction, not a clinical call.

CHST6 p.Arg278Pro

c.833G>C · rs1396230610 · VCV2269294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6846 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6846	likely pathogenic
REVEL	0.641	indeterminate
SaProt	LLR -12.90	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.1, phastCons 0.91
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	23.7	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 0.000339% European (non-Finnish) · 4/1,179,944 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,459,932 alleles · very rare

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: CHST6
Protein: p.Arg278Pro
Coding: c.833G>C
MANE Select: NM_021615
dbSNP: rs1396230610
Type: single nucleotide variant
Location: chr16:75478996 (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.Arg278Trp Uncertain significance ★ ⚠ same residue
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

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-arg278pro (accessed [today's date]).

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