Is PIGB p.Ser509= (c.1527C>T) pathogenic?

PIGB p.Ser509= (c.1527C>T) is classified Benign in PIGB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele.

PIGB p.Ser509=

Q: How common is PIGB p.Ser509= (c.1527C>T) in the general population?

PIGB p.Ser509= (c.1527C>T) is common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1527C>T · rs8043415 · VCV1577109

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 20.9%, 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 looked up on this page · why
Constraint at this position
Conservation	phyloP -0.4	GERP -2.2
Overall
CADD	7.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.9% African / African-American · 15,537/74,426 alleles

Filtering AF 20.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.5%

Overall 7.76% 124,278/1,601,842 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20.9%	5
Ashkenazi Jewishnot grpmax-eligible	11.4%	9
South Asian	11.1%	9
Middle Eastern	9.75%	10
Remaining individualsnot grpmax-eligible	8.13%	12
European (non-Finnish)	7.08%	14
Admixed American	5.61%	18
Finnishnot grpmax-eligible	5.59%	18
Amishnot grpmax-eligible	0.329%	304
East Asian	0.0447%	2,238

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: PIGB
Protein: p.Ser509=
Coding: c.1527C>T
MANE Select: NM_001204450 · reported on NM_004855
dbSNP: rs8043415
Type: single nucleotide variant
Location: chr15:55355294 (GRCh38)

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

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/pigb-p-ser509 (accessed [today's date]).

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