Is CHST8 p.Arg77= (c.229C>A) pathogenic?

CHST8 p.Arg77= (c.229C>A) is classified Likely benign in CHST8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-14). Ultra-rare (popmax 0.0921%, afr); Associated with CHST8-related disorder.

What condition is associated with CHST8 p.Arg77= (c.229C>A)?

CHST8 p.Arg77= (c.229C>A) is associated with CHST8-related disorder (ClinVar).

How common is CHST8 p.Arg77= (c.229C>A) in the general population?

CHST8 p.Arg77= (c.229C>A) is ultra-rare (popmax 0.0921%, afr) (gnomAD).

CHST8 p.Arg77=

c.229C>A · rs149660944 · VCV3035529

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0921%, afr)

Conditions

CHST8-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 -0.71	GERP -0.66
Overall
CADD	1.175	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0921% African / African-American · 69/74,896 alleles

Filtering AF 0.0746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0683%

Overall 0.00453% 73/1,609,800 alleles · ultra-rare exomes 31/1,457,480 · genomes 42/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0921%	1,085
Admixed American	0.00507%	19,741
Remaining individualsnot grpmax-eligible	0.00161%	62,304

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.Arg77=
Coding: c.229C>A
MANE Select: NM_001127895
dbSNP: rs149660944
Type: single nucleotide variant
Location: chr19:33772017 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.90
Residue 77: a UniProt-annotated variant site (according to pubmed:22289416 this variant results in decreased glycosaminoglycan sulfation; according to pubmed:28204496 it does not affect sulfotransferase activity); the 'disordered' region

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

Disease context

CHST8-related disorder

Similar variants

CHST8 p.Arg77Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
CHST8 p.Lys234= Benign same condition
CHST8 p.Pro126Arg Likely benign same condition
CHST8 p.Pro139= Likely benign same condition
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

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-arg77 (accessed [today's date]).

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