Is CHST4 p.Gln16Arg (c.47A>G) pathogenic?

CHST4 p.Gln16Arg (c.47A>G) is classified Uncertain significance in CHST4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.2694); Very rare (popmax 0.000534%, nfe).

How common is CHST4 p.Gln16Arg (c.47A>G) in the general population?

CHST4 p.Gln16Arg (c.47A>G) is very rare (popmax 0.000534%, nfe) (gnomAD).

What do computational predictors say about CHST4 p.Gln16Arg (c.47A>G)?

AlphaMissense predicts likely benign (score 0.2694) — an in-silico prediction, not a clinical call.

CHST4 p.Gln16Arg

c.47A>G · VCV4228640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000534%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2694	likely benign
REVEL	0.425	indeterminate
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,157 bp · p 0.075 · regional, not allelic
Overall
CADD	16.32	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000534% European (non-Finnish) · 6/1,124,060 alleles

Filtering AF 0.000192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000126%

Overall 0.000401% 6/1,495,820 alleles · very rare

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.Gln16Arg
Coding: c.47A>G
MANE Select: NM_001166395
Type: single nucleotide variant
Location: chr16:71536724 (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.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.Arg130Gln Uncertain significance ★ ⚠ same type
CHST4 p.Arg130Trp 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-gln16arg (accessed [today's date]).

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