Is PTGER3 p.Ser43Pro (c.127T>C) pathogenic?

PTGER3 p.Ser43Pro (c.127T>C) is classified Likely benign in PTGER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0502); Very rare (popmax 0.00167%, amr).

How common is PTGER3 p.Ser43Pro (c.127T>C) in the general population?

PTGER3 p.Ser43Pro (c.127T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PTGER3 p.Ser43Pro (c.127T>C)?

AlphaMissense predicts likely benign (score 0.0502) — an in-silico prediction, not a clinical call.

PTGER3 p.Ser43Pro

c.127T>C · VCV4573558

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0502 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0502	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -5.98	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 -0.73	GERP -3.9
Regional constraint	o/e 1.13	unconstrained · MANE · 281 bp · p 0.13 · regional, not allelic
Overall
CADD	1.374	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

Grpmax group 0.00167% Admixed American · 1/59,790 alleles

Overall 0.000124% 2/1,610,676 alleles · very rare exomes 1/1,458,472 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,790
African / African-American	0.00133%	74,924

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.Ser43Pro
Coding: c.127T>C
MANE Select: NM_198719
Type: single nucleotide variant
Location: chr1:71047451 (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.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-ser43pro (accessed [today's date]).

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