Is CHSY1 p.Ser32Pro (c.94T>C) pathogenic?

CHSY1 p.Ser32Pro (c.94T>C) is classified Uncertain significance in CHSY1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-13). AlphaMissense: likely benign (0.1992); Ultra-rare (popmax 0.0137%, sas); Associated with Inborn genetic diseases.

What condition is associated with CHSY1 p.Ser32Pro (c.94T>C)?

CHSY1 p.Ser32Pro (c.94T>C) is associated with Inborn genetic diseases, temtamy preaxial brachydactyly syndrome (ClinVar).

How common is CHSY1 p.Ser32Pro (c.94T>C) in the general population?

CHSY1 p.Ser32Pro (c.94T>C) is ultra-rare (popmax 0.0137%, sas) (gnomAD).

What do computational predictors say about CHSY1 p.Ser32Pro (c.94T>C)?

AlphaMissense predicts likely benign (score 0.1992) — an in-silico prediction, not a clinical call.

CHSY1 p.Ser32Pro

c.94T>C · rs760263900 · VCV1041711

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1992 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1992	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -5.29	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 5.5	GERP 1, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 16 kb · p 0.0015 · regional, not allelic
Overall
CADD	20.4	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 0.0137% South Asian · 8/58,510 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00493%

Overall 0.000691% 8/1,157,416 alleles · ultra-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: CHSY1
Protein: p.Ser32Pro
Coding: c.94T>C
MANE Select: NM_014918
dbSNP: rs760263900
Type: single nucleotide variant
Location: chr15:101251363 (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

Also linked: temtamy preaxial brachydactyly syndrome

Similar variants

CHSY1 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
CHSY1 p.Ala471Thr Uncertain significance ★★ ⚠ same condition
CHSY1 p.Ala61Val Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg180His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg229Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg233Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg244Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg322His 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-ser32pro (accessed [today's date]).

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