Is PTGES p.Ser61= (c.183C>T) pathogenic?

PTGES p.Ser61= (c.183C>T) is classified Benign in PTGES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-10-10). Common (popmax 8.14%, afr) — too common for a highly-penetrant pathogenic allele.

PTGES p.Ser61=

Q: How common is PTGES p.Ser61= (c.183C>T) in the general population?

PTGES p.Ser61= (c.183C>T) is common (popmax 8.14%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.183C>T · rs3205181 · VCV768328

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.14%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.7	GERP -5.1
Overall
CADD	0.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.14% African / African-American · 5,873/72,144 alleles

Filtering AF 7.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.9%

Overall 0.461% 7,281/1,579,712 alleles · common exomes 3,640/1,427,466 · genomes 3,641/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.14%	12
Middle Eastern	0.804%	124
Admixed American	0.796%	126
Remaining individualsnot grpmax-eligible	0.621%	161
East Asian	0.212%	472
Ashkenazi Jewishnot grpmax-eligible	0.116%	865
European (non-Finnish)	0.0373%	2,684
South Asian	0.0104%	9,573
Finnishnot grpmax-eligible	0.00157%	63,706

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: PTGES
Protein: p.Ser61=
Coding: c.183C>T
MANE Select: NM_004878
dbSNP: rs3205181
Type: single nucleotide variant
Location: chr9:129748681 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI 0.40 (gnomAD)
Structure: AlphaFold pLDDT 96.25 · 18 PDB

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

Similar variants

PTGES p.Ser61Gly Uncertain significance ★ ⚠ same residue
PTGES p.Arg60= Benign ★★ same type
PTGES p.Val7Glu Benign ★★ same type
PTGES p.Ala149Thr Uncertain significance ★ ⚠ same type
PTGES p.Arg67Cys Uncertain significance ★ ⚠ same type
PTGES p.Glu147Asp Uncertain significance ★ ⚠ same type
PTGES p.Gly93Ser Uncertain significance ★ ⚠ same type
PTGES p.His102Tyr 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/ptges-p-ser61 (accessed [today's date]).

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