Is CHST4 p.Arg130Gln (c.389G>A) pathogenic?

CHST4 p.Arg130Gln (c.389G>A) is classified Uncertain significance in CHST4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: likely benign (0.1513); Very rare (popmax 0.00988%, sas).

How common is CHST4 p.Arg130Gln (c.389G>A) in the general population?

CHST4 p.Arg130Gln (c.389G>A) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about CHST4 p.Arg130Gln (c.389G>A)?

AlphaMissense predicts likely benign (score 0.1513) — an in-silico prediction, not a clinical call.

CHST4 p.Arg130Gln

c.389G>A · VCV3492746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1513	likely benign
REVEL	0.816	moderately pathogenic-leaning
SaProt	LLR -6.91	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,157 bp · p 0.075 · regional, not allelic
Overall
CADD	25.6	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 0.00988% South Asian · 9/91,070 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00167% 27/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,119
African / African-American	0.00668%	14,980
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,882
European (non-Finnish)	0.000932%	107,275

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: CHST4
Protein: p.Arg130Gln
Coding: c.389G>A
MANE Select: NM_001166395
Type: single nucleotide variant
Location: chr16:71537066 (GRCh38)
Gene constraint: LOEUF 1.836 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 90.66

Full CHST4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST4 p.Arg130Trp Uncertain significance ★ ⚠ same residue
CHST4 p.Ala135Val Uncertain significance ★ ⚠ same type
CHST4 p.Ala167Ser Uncertain significance ★ ⚠ same type
CHST4 p.Ala18Ser Uncertain significance ★ ⚠ same type
CHST4 p.Ala18Thr Uncertain significance ★ ⚠ same type
CHST4 p.Ala333Val Uncertain significance ★ ⚠ same type
CHST4 p.Arg118Gln Uncertain significance ★ ⚠ same type
CHST4 p.Arg149Trp 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/chst4-p-arg130gln (accessed [today's date]).

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