Is PTGER3 p.Ser232Pro (c.694T>C) pathogenic?

PTGER3 p.Ser232Pro (c.694T>C) is classified Uncertain significance in PTGER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). AlphaMissense: likely pathogenic (0.5643); Absent from gnomAD v4.1.

How common is PTGER3 p.Ser232Pro (c.694T>C) in the general population?

PTGER3 p.Ser232Pro (c.694T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTGER3 p.Ser232Pro (c.694T>C)?

AlphaMissense predicts likely pathogenic (score 0.5643) — an in-silico prediction, not a clinical call.

PTGER3 p.Ser232Pro

c.694T>C · rs2525441443 · VCV3220726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5643 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5643	likely pathogenic
REVEL	0.246	benign-leaning
SaProt	LLR -11.53	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.46, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 35 kb · p 0.078 · regional, not allelic
Overall
CADD	24.0	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: PTGER3
Protein: p.Ser232Pro
Coding: c.694T>C
MANE Select: NM_198719
dbSNP: rs2525441443
Type: single nucleotide variant
Location: chr1:71046884 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 76.06 · 4 PDB
Residue 232: an α-helix

Full PTGER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTGER3 p.Leu37= Benign ★★ same type
PTGER3 p.Arg16His Uncertain significance ★ ⚠ same type
PTGER3 p.Arg29Leu Uncertain significance ★ ⚠ same type
PTGER3 p.Arg34Pro Uncertain significance ★ ⚠ same type
PTGER3 p.Arg361Ile Uncertain significance ★ same type
PTGER3 p.Arg361Ser Uncertain significance ★ same type
PTGER3 p.Arg39His Uncertain significance ★ ⚠ same type
PTGER3 p.Arg80Pro 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/ptger3-p-ser232pro (accessed [today's date]).

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