Is CHST8 p.Leu288= (c.864G>T) pathogenic?

CHST8 p.Leu288= (c.864G>T) is classified Benign in CHST8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-04). Common (popmax 12.3%, afr) — too common for a highly-penetrant pathogenic allele.

CHST8 p.Leu288=

Q: How common is CHST8 p.Leu288= (c.864G>T) in the general population?

CHST8 p.Leu288= (c.864G>T) is common (popmax 12.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.864G>T · rs61733524 · VCV1225863

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 12.3%, afr) — too common for a highly-penetrant pathogenic allele

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 1.7	GERP 0.1, phastCons 1
Overall
CADD	7.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.3% African / African-American · 9,224/75,046 alleles

Filtering AF 12.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 12%

Overall 0.657% 10,605/1,613,894 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.3%	8
Admixed American	0.876%	114
Remaining individualsnot grpmax-eligible	0.838%	119
Middle Eastern	0.264%	379
South Asian	0.0285%	3,503
European (non-Finnish)	0.0245%	4,083

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: CHST8
Protein: p.Leu288=
Coding: c.864G>T
MANE Select: NM_001127895
dbSNP: rs61733524
Type: single nucleotide variant
Location: chr19:33772652 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.90

Full CHST8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST8 p.Val186Ala Uncertain significance ★★ ⚠ same type
CHST8 c.168+64G>A Benign ★★ same type
CHST8 c.-86-36C>T Benign ★★ same type
CHST8 p.Arg9= Benign ★★ same type
CHST8 p.Ala23Gly Uncertain significance ★ ⚠ same type
CHST8 p.Ala293Pro Uncertain significance ★ ⚠ same type
CHST8 p.Ala293Ser Uncertain significance ★ ⚠ same type
CHST8 p.Ala381Thr Uncertain significance ★ ⚠ same type

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/chst8-p-leu288 (accessed [today's date]).

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