Is CTPS1 p.Pro196= (c.588T>C) pathogenic?

CTPS1 p.Pro196= (c.588T>C) is classified Likely benign in CTPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). Very rare (popmax 8.52e-05%, nfe); Associated with combined immunodeficiency due to CTPS1 deficiency.

What condition is associated with CTPS1 p.Pro196= (c.588T>C)?

CTPS1 p.Pro196= (c.588T>C) is associated with combined immunodeficiency due to CTPS1 deficiency (ClinVar).

How common is CTPS1 p.Pro196= (c.588T>C) in the general population?

CTPS1 p.Pro196= (c.588T>C) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

CTPS1 p.Pro196=

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.588T>C · VCV3612976

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

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 -1.6	GERP -5.2
Overall
CADD	8.051	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,860 alleles

Overall 0.000209% 3/1,438,350 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00325%	30,778
European (non-Finnish)grpmax	8.52e-05%	1,173,860

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CTPS1
Protein: p.Pro196=
Coding: c.588T>C
MANE Select: NM_001905
Type: single nucleotide variant
Location: chr1:40991197 (GRCh38)
Gene constraint: LOEUF 0.423 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.46 · 7 PDB
Residue 196: an α-helix

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 p.Pro196Ser Uncertain significance ★ ⚠ same residue
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

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-pro196 (accessed [today's date]).

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