Is CHSY1 p.Phe482Ser (c.1445T>C) pathogenic?

CHSY1 p.Phe482Ser (c.1445T>C) is classified Uncertain significance in CHSY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: ambiguous (0.5257); Ultra-rare (popmax 0.0209%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHSY1 p.Phe482Ser (c.1445T>C)?

CHSY1 p.Phe482Ser (c.1445T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHSY1 p.Phe482Ser (c.1445T>C) in the general population?

CHSY1 p.Phe482Ser (c.1445T>C) is ultra-rare (popmax 0.0209%, nfe) (gnomAD).

What do computational predictors say about CHSY1 p.Phe482Ser (c.1445T>C)?

AlphaMissense predicts ambiguous (score 0.5257) — an in-silico prediction, not a clinical call.

CHSY1 p.Phe482Ser

c.1445T>C · VCV3833300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5257 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5257	ambiguous
REVEL	0.402	indeterminate
SaProt	LLR -5.35	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 58 kb · p 0.004 · regional, not allelic
Overall
CADD	24.0	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 0.0209% European (non-Finnish) · 245/1,174,940 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.0164% 264/1,607,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0209%	4,796
Remaining individualsnot grpmax-eligible	0.0193%	5,179
African / African-American	0.00536%	18,671
Admixed American	0.00502%	19,923

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: CHSY1
Protein: p.Phe482Ser
Coding: c.1445T>C
MANE Select: NM_014918
Type: single nucleotide variant
Location: chr15:101178352 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.20

Full CHSY1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHSY1 p.Ala471Thr Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg180His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg229Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg322His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg336Cys Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg368His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg423Gly Uncertain significance ★★ ⚠ same condition
CHSY1 p.Asn85Asp Uncertain significance ★★ ⚠ same condition

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/chsy1-p-phe482ser (accessed [today's date]).

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