Is PTGES2 p.Ile150Met (c.450C>G) pathogenic?

PTGES2 p.Ile150Met (c.450C>G) is classified Uncertain significance in PTGES2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: ambiguous (0.4537); Absent from gnomAD v4.1.

How common is PTGES2 p.Ile150Met (c.450C>G) in the general population?

PTGES2 p.Ile150Met (c.450C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTGES2 p.Ile150Met (c.450C>G)?

AlphaMissense predicts ambiguous (score 0.4537) — an in-silico prediction, not a clinical call.

PTGES2 p.Ile150Met

c.450C>G · VCV3784806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4537 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4537	ambiguous
REVEL	0.298	indeterminate
SaProt	LLR -12.38	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP 4.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,569 bp · p 0.85 · regional, not allelic
Overall
CADD	24.5	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

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: PTGES2
Protein: p.Ile150Met
Coding: c.450C>G
MANE Select: NM_025072
Type: single nucleotide variant
Location: chr9:128125271 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.07
Residue 150: the glutaredoxin domain

Full PTGES2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTGES2 p.Lys269Asn Benign ★★ same type
PTGES2 p.Ala10Gly Uncertain significance ★ ⚠ same type
PTGES2 p.Ala171Ser Uncertain significance ★ ⚠ same type
PTGES2 p.Ala238Val Uncertain significance ★ ⚠ same type
PTGES2 p.Ala259Val Uncertain significance ★ ⚠ same type
PTGES2 p.Ala284Val Uncertain significance ★ ⚠ same type
PTGES2 p.Arg117Gln Uncertain significance ★ ⚠ same type
PTGES2 p.Arg136His 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/ptges2-p-ile150met (accessed [today's date]).

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