Is CHSY1 p.Ser325= (c.975C>T) pathogenic?

CHSY1 p.Ser325= (c.975C>T) is classified Benign/Likely benign in CHSY1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-01). Rare (popmax 0.41%, afr); Associated with temtamy preaxial brachydactyly syndrome.

What condition is associated with CHSY1 p.Ser325= (c.975C>T)?

CHSY1 p.Ser325= (c.975C>T) is associated with temtamy preaxial brachydactyly syndrome (ClinVar).

How common is CHSY1 p.Ser325= (c.975C>T) in the general population?

CHSY1 p.Ser325= (c.975C>T) is rare (popmax 0.41%, afr) (gnomAD).

CHSY1 p.Ser325=

c.975C>T · rs142783588 · VCV1598789

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.41%, afr)

Conditions

temtamy preaxial brachydactyly syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.8	GERP -3.8
Overall
CADD	2.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.41% African / African-American · 308/75,032 alleles

Filtering AF 0.373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.358%

Overall 0.0256% 413/1,614,178 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.41%	244
Remaining individualsnot grpmax-eligible	0.0432%	2,315
South Asian	0.0417%	2,397
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
Middle Eastern	0.033%	3,031
Admixed American	0.025%	4,002
East Asian	0.00446%	22,441
European (non-Finnish)	0.000763%	131,115

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.Ser325=
Coding: c.975C>T
MANE Select: NM_014918
dbSNP: rs142783588
Type: single nucleotide variant
Location: chr15:101178822 (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

temtamy preaxial brachydactyly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHSY1 p.Ser325Thr Uncertain significance ★★ ⚠ same residue
CHSY1 p.Ala263Ser 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-ser325 (accessed [today's date]).

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