Is PTGER3 p.Arg34Pro (c.101G>C) pathogenic?

PTGER3 p.Arg34Pro (c.101G>C) is classified Uncertain significance in PTGER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely benign (0.076); Ultra-rare (popmax 0.02%, afr).

How common is PTGER3 p.Arg34Pro (c.101G>C) in the general population?

PTGER3 p.Arg34Pro (c.101G>C) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about PTGER3 p.Arg34Pro (c.101G>C)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

PTGER3 p.Arg34Pro

c.101G>C · VCV4573555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.50	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 -2.3	GERP -1.9
Regional constraint	o/e 1.13	unconstrained · MANE · 281 bp · p 0.13 · regional, not allelic
Overall
CADD	11.13	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

Grpmax group 0.02% African / African-American · 15/74,934 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.000995% 16/1,607,830 alleles · ultra-rare exomes 7/1,455,598 · genomes 9/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,996
Remaining individualsnot grpmax-eligible	0.00161%	62,232

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: PTGER3
Protein: p.Arg34Pro
Coding: c.101G>C
MANE Select: NM_198719
Type: single nucleotide variant
Location: chr1:71047477 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 76.06 · 4 PDB

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.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
PTGER3 p.Cys371Tyr 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-arg34pro (accessed [today's date]).

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