Is PIGB p.Ser535= (c.1605T>C) pathogenic?

PIGB p.Ser535= (c.1605T>C) is classified Likely benign in PIGB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). Very rare (popmax 0.00802%, afr).

How common is PIGB p.Ser535= (c.1605T>C) in the general population?

PIGB p.Ser535= (c.1605T>C) is very rare (popmax 0.00802%, afr) (gnomAD).

PIGB p.Ser535=

c.1605T>C · rs746164541 · VCV2060262

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00802%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 1.8	GERP 4.4, phastCons 1
Overall
CADD	8.929	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00802% African / African-American · 6/74,848 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,611,550 alleles · very rare exomes 2/1,459,352 · genomes 4/152,198 · joint denominator

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.Ser535=
Coding: c.1605T>C
MANE Select: NM_004855
dbSNP: rs746164541
Type: single nucleotide variant
Location: chr15:55355372 (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-ser535 (accessed [today's date]).

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