Is CHST8 p.Pro126Arg (c.377C>G) pathogenic?

CHST8 p.Pro126Arg (c.377C>G) is classified Likely benign in CHST8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0613); Rare (popmax 0.208%, amr); Associated with CHST8-related disorder.

What condition is associated with CHST8 p.Pro126Arg (c.377C>G)?

CHST8 p.Pro126Arg (c.377C>G) is associated with CHST8-related disorder (ClinVar).

How common is CHST8 p.Pro126Arg (c.377C>G) in the general population?

CHST8 p.Pro126Arg (c.377C>G) is rare (popmax 0.208%, amr) (gnomAD).

What do computational predictors say about CHST8 p.Pro126Arg (c.377C>G)?

AlphaMissense predicts likely benign (score 0.0613) — an in-silico prediction, not a clinical call.

CHST8 p.Pro126Arg

c.377C>G · VCV3353231

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0613 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.208%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CHST8-related disorder

Computational evidence

Protein change
AlphaMissense	0.0613	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.5	GERP -3.1
Regional constraint	o/e 1.04	unconstrained · MANE · 84 kb · p 0.3 · regional, not allelic
Overall
CADD	0.327	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

Grpmax group 0.208% Admixed American · 122/58,598 alleles

Filtering AF 0.178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.00787% 126/1,600,954 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.208%	480
Remaining individualsnot grpmax-eligible	0.00485%	20,620
European (non-Finnish)	8.51e-05%	1,175,206

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.Pro126Arg
Coding: c.377C>G
MANE Select: NM_001127895
Type: single nucleotide variant
Location: chr19:33772165 (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

Disease context

CHST8-related disorder

Similar variants

CHST8 p.Arg77= Likely benign same condition
CHST8 p.Lys234= 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
CHST8 p.Leu288= 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-pro126arg (accessed [today's date]).

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