Is CTPS1 p.Ser187= (c.561T>C) pathogenic?

CTPS1 p.Ser187= (c.561T>C) is classified Likely benign in CTPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Absent from gnomAD v4.1; Associated with combined immunodeficiency due to CTPS1 deficiency.

What condition is associated with CTPS1 p.Ser187= (c.561T>C)?

CTPS1 p.Ser187= (c.561T>C) is associated with combined immunodeficiency due to CTPS1 deficiency (ClinVar).

How common is CTPS1 p.Ser187= (c.561T>C) in the general population?

CTPS1 p.Ser187= (c.561T>C) is absent from gnomAD v4.1 (gnomAD).

CTPS1 p.Ser187=

Q: How is Severe combined immunodeficiency due to CTPS1 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.561T>C · rs2524276913 · VCV2827750

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,898)

Conditions

combined immunodeficiency due to CTPS1 deficiency

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 2.8	GERP 0.4, phastCons 1
Overall
CADD	12.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,578,898). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTPS1
Protein: p.Ser187=
Coding: c.561T>C
MANE Select: NM_001905
dbSNP: rs2524276913
Type: single nucleotide variant
Location: chr1:40991170 (GRCh38)
Gene constraint: LOEUF 0.423 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.46 · 7 PDB
Residue 187: a turn

Full CTPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to CTPS1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to CTPS1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

CTPS1 c.1692-1G>C Pathogenic ★★ same condition
CTPS1 c.1095-5T>G Uncertain significance ★★ same condition
CTPS1 p.Ala471Thr Uncertain significance ★★ ⚠ same condition
CTPS1 p.Arg102Trp Uncertain significance ★★ ⚠ same condition
CTPS1 p.Arg294His Uncertain significance ★★ ⚠ same condition
CTPS1 p.Arg376Gln Uncertain significance ★★ ⚠ same condition
CTPS1 p.Arg550Gln Uncertain significance ★★ ⚠ same condition
CTPS1 p.Asn412Ser 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/ctps1-p-ser187 (accessed [today's date]).

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