Is PTGS1 p.Pro504= (c.1512T>C) pathogenic?

PTGS1 p.Pro504= (c.1512T>C) is classified Benign in PTGS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). Common (popmax 26.6%, afr) — too common for a highly-penetrant pathogenic allele.

PTGS1 p.Pro504=

Q: How common is PTGS1 p.Pro504= (c.1512T>C) in the general population?

PTGS1 p.Pro504= (c.1512T>C) is common (popmax 26.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1512T>C · VCV4683427

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 26.6%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.4
Overall
CADD	0.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.6% African / African-American · 19,959/74,932 alleles

Filtering AF 26.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.2%

Overall 1.74% 28,052/1,613,186 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	26.6%	4
Middle Eastern	6.01%	17
Remaining individualsnot grpmax-eligible	2.59%	39
Admixed American	2.42%	41
Ashkenazi Jewishnot grpmax-eligible	2.19%	46
South Asian	0.779%	128
European (non-Finnish)	0.276%	362
Finnishnot grpmax-eligible	0.0625%	1,601
East Asian	0.0112%	8,963

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: PTGS1
Protein: p.Pro504=
Coding: c.1512T>C
MANE Select: NM_000962
Type: single nucleotide variant
Location: chr9:122392256 (GRCh38)
Gene constraint: LOEUF 0.82 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.19 · 1 PDB
Residue 504: an α-helix

Full PTGS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTGS1 p.Gln240Pro Uncertain significance ★★ ⚠ same type
PTGS1 c.762+10G>A Benign ★★ same type
PTGS1 p.Ala499= Benign ★★ same type
PTGS1 p.Cys68= Benign ★★ same type
PTGS1 p.Gln41= Benign ★★ same type
PTGS1 p.Val481Ile Likely benign ★★ same type
PTGS1 p.Arg108Ter Uncertain significance ★ same type
PTGS1 p.Arg178Cys 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/ptgs1-p-pro504 (accessed [today's date]).

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