Is CHST6 p.His249= (c.747C>T) pathogenic?

CHST6 p.His249= (c.747C>T) is classified Likely benign in CHST6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-28). Very rare (popmax 0.0033%, sas); Associated with CHST6-related disorder.

What condition is associated with CHST6 p.His249= (c.747C>T)?

CHST6 p.His249= (c.747C>T) is associated with CHST6-related disorder (ClinVar).

How common is CHST6 p.His249= (c.747C>T) in the general population?

CHST6 p.His249= (c.747C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

CHST6 p.His249=

c.747C>T · rs545496065 · VCV3044132

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Conditions

CHST6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.7
Overall
CADD	7.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/91,002 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000374% 6/1,605,696 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,334
East Asian	0.00223%	44,858
European (non-Finnish)	0.00017%	589,619

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.His249=
Coding: c.747C>T
MANE Select: NM_021615
dbSNP: rs545496065
Type: single nucleotide variant
Location: chr16:75479082 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66
Residue 249: a UniProt-annotated variant site (in mcd)

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

Disease context

CHST6-related disorder

Similar variants

CHST6 p.His249Gln Uncertain significance ★ ⚠ same residue
CHST6 p.Ala128Thr Likely pathogenic ★★ ⚠ same condition
CHST6 p.Arg127Cys Pathogenic ★★ same condition
CHST6 p.Glu274Lys Pathogenic ★★ same condition
CHST6 p.Leu200Arg Pathogenic ★★ same condition
CHST6 p.Ala128Val Pathogenic ★ same condition
CHST6 p.Ser131Leu Pathogenic ★ same condition
CHST6 p.Ser210Phe Likely pathogenic ★ 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-his249 (accessed [today's date]).

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