Is CHST8 p.His319Pro (c.956A>C) pathogenic?

CHST8 p.His319Pro (c.956A>C) is classified Uncertain significance in CHST8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: ambiguous (0.5481); Absent from gnomAD v4.1.

How common is CHST8 p.His319Pro (c.956A>C) in the general population?

CHST8 p.His319Pro (c.956A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHST8 p.His319Pro (c.956A>C)?

AlphaMissense predicts ambiguous (score 0.5481) — an in-silico prediction, not a clinical call.

CHST8 p.His319Pro

c.956A>C · VCV4228672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5481 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5481	ambiguous
REVEL	0.741	pathogenic-leaning
SaProt	LLR -9.62	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 84 kb · p 0.3 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHST8
Protein: p.His319Pro
Coding: c.956A>C
MANE Select: NM_001127895
Type: single nucleotide variant
Location: chr19:33772744 (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

Similar variants

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
CHST8 p.Ala23Gly Uncertain significance ★ ⚠ same type
CHST8 p.Ala293Pro Uncertain significance ★ ⚠ same type
CHST8 p.Ala293Ser 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/chst8-p-his319pro (accessed [today's date]).

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