Is CHST13 p.Pro256Arg (c.767C>G) pathogenic?

CHST13 p.Pro256Arg (c.767C>G) is classified Uncertain significance in CHST13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.9338); Very rare (popmax 0.00198%, nfe).

How common is CHST13 p.Pro256Arg (c.767C>G) in the general population?

CHST13 p.Pro256Arg (c.767C>G) is very rare (popmax 0.00198%, nfe) (gnomAD).

What do computational predictors say about CHST13 p.Pro256Arg (c.767C>G)?

AlphaMissense predicts likely pathogenic (score 0.9338) — an in-silico prediction, not a clinical call.

CHST13 p.Pro256Arg

c.767C>G · VCV3833252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00198%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9338	likely pathogenic
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -16.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP 2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 18 kb · p 0.0045 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00198% European (non-Finnish) · 23/1,160,682 alleles

Filtering AF 0.00132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0011%

Overall 0.00147% 23/1,568,850 alleles · very rare exomes 23/1,416,796 · genomes 0/152,054 · joint denominator

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: CHST13
Protein: p.Pro256Arg
Coding: c.767C>G
MANE Select: NM_152889
Type: single nucleotide variant
Location: chr3:126542319 (GRCh38)

Full CHST13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/chst13-p-pro256arg (accessed [today's date]).

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