Is PTGS2 p.Asp300= (c.900T>C) pathogenic?

PTGS2 p.Asp300= (c.900T>C) is classified Benign in PTGS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-04). Common (popmax 5.95%, afr) — too common for a highly-penetrant pathogenic allele.

PTGS2 p.Asp300=

Q: How common is PTGS2 p.Asp300= (c.900T>C) in the general population?

PTGS2 p.Asp300= (c.900T>C) is common (popmax 5.95%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.900T>C · rs5278 · VCV780291

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.95%, 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 -2.1
Overall
CADD	1.264	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.95% African / African-American · 4,464/74,994 alleles

Filtering AF 5.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.75%

Overall 0.348% 5,622/1,614,096 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.95%	17
East Asian	0.983%	102
Remaining individualsnot grpmax-eligible	0.507%	197
Admixed American	0.46%	217
Middle Eastern	0.297%	337
European (non-Finnish)	0.00839%	11,919
South Asian	0.00769%	13,011

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: PTGS2
Protein: p.Asp300=
Coding: c.900T>C
MANE Select: NM_000963
dbSNP: rs5278
Type: single nucleotide variant
Location: chr1:186676537 (GRCh38)
Gene constraint: LOEUF 0.33 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.37 · 7 PDB
Residue 300: an α-helix

Full PTGS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTGS2 p.Asp300Asn Uncertain significance ★ ⚠ same residue
PTGS2 p.Arg585= Benign ★★ same type
PTGS2 p.His403= Benign ★★ same type
PTGS2 p.Ala436Ser Uncertain significance ★ ⚠ same type
PTGS2 p.Ala475Thr Uncertain significance ★ ⚠ same type
PTGS2 p.Ala529Ser Uncertain significance ★ ⚠ same type
PTGS2 p.Ala529Val Uncertain significance ★ ⚠ same type
PTGS2 p.Ala581Gly 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/ptgs2-p-asp300 (accessed [today's date]).

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