Is CTPS2 p.Arg202Cys (c.604C>T) pathogenic?

CTPS2 p.Arg202Cys (c.604C>T) is classified Uncertain significance in CTPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.2571); Very rare (popmax 0.00593%, eas).

How common is CTPS2 p.Arg202Cys (c.604C>T) in the general population?

CTPS2 p.Arg202Cys (c.604C>T) is very rare (popmax 0.00593%, eas) (gnomAD).

What do computational predictors say about CTPS2 p.Arg202Cys (c.604C>T)?

AlphaMissense predicts likely benign (score 0.2571) — an in-silico prediction, not a clinical call.

CTPS2 p.Arg202Cys

c.604C>T · VCV4235761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2571 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2571	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -11.61	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 112 kb · p 2.2e-14 · regional, not allelic
Overall
CADD	24.8	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 0.00593% East Asian · 2/33,733 alleles

Filtering AF 0.000982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000828% 10/1,208,069 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00593%	16,867
South Asian	0.00176%	56,710
European (non-Finnish)	0.000783%	127,742

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: CTPS2
Protein: p.Arg202Cys
Coding: c.604C>T
MANE Select: NM_175859
Type: single nucleotide variant
Location: chrX:16693176 (GRCh38)
Structure: AlphaFold pLDDT 91.79 · 8 PDB
Residue 202: an α-helix

Full CTPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTPS2 p.Gly542= Benign ★★ same type
CTPS2 p.Ala315Thr Conflicting classifications of pathogenicity ★ ⚠ same type
CTPS2 p.Ala428Val Uncertain significance ★ ⚠ same type
CTPS2 p.Ala546Thr Uncertain significance ★ ⚠ same type
CTPS2 p.Arg217Gln Uncertain significance ★ ⚠ same type
CTPS2 p.Arg481Gln Uncertain significance ★ ⚠ same type
CTPS2 p.Arg481Trp Uncertain significance ★ ⚠ same type
CTPS2 p.Asn99His Uncertain significance ★ ⚠ same type

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/ctps2-p-arg202cys (accessed [today's date]).

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