Is BPIFB2 p.Arg47Trp (c.139C>T) pathogenic?

BPIFB2 p.Arg47Trp (c.139C>T) is classified Uncertain significance in BPIFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.1312); Ultra-rare (popmax 0.029%, eas).

How common is BPIFB2 p.Arg47Trp (c.139C>T) in the general population?

BPIFB2 p.Arg47Trp (c.139C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about BPIFB2 p.Arg47Trp (c.139C>T)?

AlphaMissense predicts likely benign (score 0.1312) — an in-silico prediction, not a clinical call.

BPIFB2 p.Arg47Trp

c.139C>T · rs372044696 · VCV2302268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1312 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1312	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.17	GERP -1.3, phastCons 0.005
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.62 · regional, not allelic
Overall
CADD	24.0	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 0.029% East Asian · 13/44,844 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00626% 101/1,614,004 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,450
South Asian	0.0187%	5,357
African / African-American	0.008%	12,506
European (non-Finnish)	0.00508%	19,666
Remaining individualsnot grpmax-eligible	0.0048%	20,833
Admixed American	0.00333%	30,006

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: BPIFB2
Protein: p.Arg47Trp
Coding: c.139C>T
MANE Select: NM_025227
dbSNP: rs372044696
Type: single nucleotide variant
Location: chr20:33011053 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.04

Full BPIFB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BPIFB2 p.Arg47Gln Uncertain significance ★ ⚠ same residue
BPIFB2 p.Ala104Ser Uncertain significance ★ ⚠ same type
BPIFB2 p.Ala104Thr Uncertain significance ★ ⚠ same type
BPIFB2 p.Ala144Thr Uncertain significance ★ ⚠ same type
BPIFB2 p.Ala267Val Uncertain significance ★ ⚠ same type
BPIFB2 p.Ala274Thr Uncertain significance ★ ⚠ same type
BPIFB2 p.Ala420Val Uncertain significance ★ ⚠ same type
BPIFB2 p.Ala48Ser 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/bpifb2-p-arg47trp (accessed [today's date]).

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