Is CTPS2 p.Asp290Tyr (c.868G>T) pathogenic?

CTPS2 p.Asp290Tyr (c.868G>T) is classified Uncertain significance in CTPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: likely benign (0.1867); Absent from gnomAD v4.1.

How common is CTPS2 p.Asp290Tyr (c.868G>T) in the general population?

CTPS2 p.Asp290Tyr (c.868G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTPS2 p.Asp290Tyr (c.868G>T)?

AlphaMissense predicts likely benign (score 0.1867) — an in-silico prediction, not a clinical call.

CTPS2 p.Asp290Tyr

c.868G>T · rs1923514111 · VCV2283206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1867 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1867	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -9.17	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 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 112 kb · p 2.2e-14 · regional, not allelic
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTPS2
Protein: p.Asp290Tyr
Coding: c.868G>T
MANE Select: NM_175859
dbSNP: rs1923514111
Type: single nucleotide variant
Location: chrX:16689454 (GRCh38)
Structure: AlphaFold pLDDT 91.79 · 8 PDB
Residue 290: 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.Arg202Cys 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

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-asp290tyr (accessed [today's date]).

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