Is PIGB p.Pro263Ser (c.787C>T) pathogenic?

PIGB p.Pro263Ser (c.787C>T) is classified Uncertain significance in PIGB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). AlphaMissense: likely benign (0.2066); Very rare (popmax 0.00538%, afr).

How common is PIGB p.Pro263Ser (c.787C>T) in the general population?

PIGB p.Pro263Ser (c.787C>T) is very rare (popmax 0.00538%, afr) (gnomAD).

What do computational predictors say about PIGB p.Pro263Ser (c.787C>T)?

AlphaMissense predicts likely benign (score 0.2066) — an in-silico prediction, not a clinical call.

PIGB p.Pro263Ser

c.787C>T · rs761252838 · VCV2125155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00538%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2066	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -13.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 5.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.4 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00538% African / African-American · 4/74,282 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.000251% 4/1,596,144 alleles · very rare exomes 4/1,443,850 · genomes 0/152,294 · 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.Pro263Ser
Coding: c.787C>T
MANE Select: NM_004855
dbSNP: rs761252838
Type: single nucleotide variant
Location: chr15:55334000 (GRCh38)
Gene constraint: LOEUF 1.098 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.48
Residue 263: a UniProt-annotated variant site (in dee80; uncertain significance)

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

Similar variants

PIGB c.795-1G>C Likely pathogenic ★★ same type
PIGB c.795-2A>G Likely pathogenic ★★ same type
PIGB c.847-10A>G Pathogenic ★★ same type
PIGB p.Asp155His Likely pathogenic ★★ same type
PIGB p.Leu131Ter Pathogenic ★★ same type
PIGB p.Lys31Ter Pathogenic ★★ same type
PIGB p.Ala400Thr Uncertain significance ★★ ⚠ same type
PIGB p.Arg339Trp 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/pigb-p-pro263ser (accessed [today's date]).

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