Is PIGB p.Pro209= (c.627T>G) pathogenic?

PIGB p.Pro209= (c.627T>G) is classified Likely benign in PIGB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-17). Ultra-rare (popmax 0.0174%, afr); Associated with Inborn genetic diseases.

What condition is associated with PIGB p.Pro209= (c.627T>G)?

PIGB p.Pro209= (c.627T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PIGB p.Pro209= (c.627T>G) in the general population?

PIGB p.Pro209= (c.627T>G) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

PIGB p.Pro209=

c.627T>G · rs374797042 · VCV1968684

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Conditions

Inborn genetic diseases

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 0.17	GERP 3.2, phastCons 0.034
Overall
CADD	8.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,542 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00816%

Overall 0.000876% 14/1,597,914 alleles · ultra-rare exomes 6/1,445,720 · genomes 8/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,734
Remaining individualsnot grpmax-eligible	0.00161%	61,920

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.Pro209=
Coding: c.627T>G
MANE Select: NM_004855
dbSNP: rs374797042
Type: single nucleotide variant
Location: chr15:55329828 (GRCh38)
Gene constraint: LOEUF 1.098 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.48
Residue 209: a UniProt-annotated variant site (in dee80; uncertain significance)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGB p.Pro209Thr Uncertain significance ★ same residue
PIGB p.Ala400Thr Uncertain significance ★★ ⚠ same condition
PIGB p.Arg339Trp Uncertain significance ★★ ⚠ same condition
PIGB p.Asn482Lys Uncertain significance ★★ ⚠ same condition
PIGB p.Cys180Ser Uncertain significance ★★ ⚠ same condition
PIGB p.Gln419Arg Uncertain significance ★★ ⚠ same condition
PIGB p.Glu359Lys Uncertain significance ★★ ⚠ same condition
PIGB p.Gly102Ser Uncertain significance ★★ same condition

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-pro209 (accessed [today's date]).

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