Is PTGER1 p.Pro172Arg (c.515C>G) pathogenic?

PTGER1 p.Pro172Arg (c.515C>G) is classified Uncertain significance in PTGER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely pathogenic (0.9529); Very rare (popmax 0.00157%, nfe).

How common is PTGER1 p.Pro172Arg (c.515C>G) in the general population?

PTGER1 p.Pro172Arg (c.515C>G) is very rare (popmax 0.00157%, nfe) (gnomAD).

What do computational predictors say about PTGER1 p.Pro172Arg (c.515C>G)?

AlphaMissense predicts likely pathogenic (score 0.9529) — an in-silico prediction, not a clinical call.

PTGER1 p.Pro172Arg

c.515C>G · VCV4147061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00157%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9529	likely pathogenic · top 7% in PTGER1
REVEL	0.369	indeterminate
SaProt	LLR -15.56	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,757 bp · p 0.14 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00157% European (non-Finnish) · 17/1,079,428 alleles

Filtering AF 0.000959% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000784%

Overall 0.00121% 17/1,405,470 alleles · very rare exomes 16/1,254,750 · genomes 1/150,720 · joint denominator

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: PTGER1
Protein: p.Pro172Arg
Coding: c.515C>G
MANE Select: NM_000955
Type: single nucleotide variant
Location: chr19:14473806 (GRCh38)
Gene constraint: LOEUF 1.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.11 · 1 PDB
Residue 172: an α-helix

Full PTGER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTGER1 p.Ala147Val Uncertain significance ★ ⚠ same type
PTGER1 p.Ala154Thr Uncertain significance ★ ⚠ same type
PTGER1 p.Ala160Val Uncertain significance ★ ⚠ same type
PTGER1 p.Ala165Asp Uncertain significance ★ ⚠ same type
PTGER1 p.Ala19Thr Uncertain significance ★ ⚠ same type
PTGER1 p.Ala19Val Uncertain significance ★ ⚠ same type
PTGER1 p.Ala204Thr Uncertain significance ★ ⚠ same type
PTGER1 p.Ala34Gly 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/ptger1-p-pro172arg (accessed [today's date]).

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