Is BPIFB3 p.Pro267Ser (c.799C>T) pathogenic?

BPIFB3 p.Pro267Ser (c.799C>T) is classified Uncertain significance in BPIFB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.1828); Ultra-rare (popmax 0.02%, amr).

How common is BPIFB3 p.Pro267Ser (c.799C>T) in the general population?

BPIFB3 p.Pro267Ser (c.799C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about BPIFB3 p.Pro267Ser (c.799C>T)?

AlphaMissense predicts likely benign (score 0.1828) — an in-silico prediction, not a clinical call.

BPIFB3 p.Pro267Ser

c.799C>T · rs201111989 · VCV3134842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1828 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1828	likely benign
REVEL	0.248	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 18 kb · p 0.14 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P271S vs ClinVar P267S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,992 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00939%

Overall 0.00948% 153/1,613,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,999
European (non-Finnish)	0.0116%	8,613
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00134%	74,894

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: BPIFB3
Protein: p.Pro267Ser
Coding: c.799C>T
MANE Select: NM_001376932
dbSNP: rs201111989
Type: single nucleotide variant
Location: chr20:33064732 (GRCh38)
Gene constraint: LOEUF 1.158 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.71

Full BPIFB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BPIFB3 p.Ala134Ser Uncertain significance ★ ⚠ same type
BPIFB3 p.Ala134Val Uncertain significance ★ ⚠ same type
BPIFB3 p.Ala135Val Uncertain significance ★ ⚠ same type
BPIFB3 p.Ala144Ser Uncertain significance ★ ⚠ same type
BPIFB3 p.Ala211Val Uncertain significance ★ ⚠ same type
BPIFB3 p.Ala28Ser Uncertain significance ★ ⚠ same type
BPIFB3 p.Ala28Thr Uncertain significance ★ ⚠ same type
BPIFB3 p.Ala317Thr 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/bpifb3-p-pro267ser (accessed [today's date]).

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