Is CHST15 p.Lys280Arg (c.839A>G) pathogenic?

CHST15 p.Lys280Arg (c.839A>G) is classified Uncertain significance in CHST15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.075); Very rare (popmax 0.00407%, afr).

How common is CHST15 p.Lys280Arg (c.839A>G) in the general population?

CHST15 p.Lys280Arg (c.839A>G) is very rare (popmax 0.00407%, afr) (gnomAD).

What do computational predictors say about CHST15 p.Lys280Arg (c.839A>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

CHST15 p.Lys280Arg

c.839A>G · VCV4228599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.41	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 2.8	GERP 0.56, phastCons 1
Regional constraint	o/e 1.37	unconstrained · MANE · 246 bp · p 5.2e-05 · regional, not allelic
Overall
CADD	17.94	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 0.00407% African / African-American · 3/73,682 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0005%

Overall 0.000189% 3/1,589,554 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: CHST15
Protein: p.Lys280Arg
Coding: c.839A>G
MANE Select: NM_001270764
Type: single nucleotide variant
Location: chr10:124044627 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.20

Full CHST15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST15 p.Ala16Thr Benign ★★ same type
CHST15 p.Arg224= Benign ★★ same type
CHST15 p.Ala241Val Uncertain significance ★ ⚠ same type
CHST15 p.Ala283Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala321Thr Uncertain significance ★ ⚠ same type
CHST15 p.Ala330Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala357Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala412Thr 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/chst15-p-lys280arg (accessed [today's date]).

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