Is CHSY3 p.Pro483Ser (c.1447C>T) pathogenic?

CHSY3 p.Pro483Ser (c.1447C>T) is classified Uncertain significance in CHSY3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.4148); Very rare (popmax 8.49e-05%, nfe).

How common is CHSY3 p.Pro483Ser (c.1447C>T) in the general population?

CHSY3 p.Pro483Ser (c.1447C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about CHSY3 p.Pro483Ser (c.1447C>T)?

AlphaMissense predicts ambiguous (score 0.4148) — an in-silico prediction, not a clinical call.

CHSY3 p.Pro483Ser

c.1447C>T · VCV4002843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4148 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4148	ambiguous
REVEL	0.185	benign-leaning
SaProt	LLR -7.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 985 bp · p 0.77 · regional, not allelic
Overall
CADD	24.7	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 8.49e-05% European (non-Finnish) · 1/1,178,528 alleles

Overall 6.85e-05% 1/1,460,210 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: CHSY3
Protein: p.Pro483Ser
Coding: c.1447C>T
MANE Select: NM_175856
Type: single nucleotide variant
Location: chr5:130184589 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.97 · 2 PDB

Full CHSY3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHSY3 p.Ala141Thr Uncertain significance ★ ⚠ same type
CHSY3 p.Ala164Asp Uncertain significance ★ same type
CHSY3 p.Ala225Gly Uncertain significance ★ ⚠ same type
CHSY3 p.Ala53Val Uncertain significance ★ ⚠ same type
CHSY3 p.Ala793Thr Uncertain significance ★ ⚠ same type
CHSY3 p.Ala859Thr Uncertain significance ★ ⚠ same type
CHSY3 p.Arg112Gln Uncertain significance ★ ⚠ same type
CHSY3 p.Arg145Trp 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/chsy3-p-pro483ser (accessed [today's date]).

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