Is BPIFB2 p.Ser138Phe (c.413C>T) pathogenic?

BPIFB2 p.Ser138Phe (c.413C>T) is classified Likely benign in BPIFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.0974); Absent from gnomAD v4.1.

How common is BPIFB2 p.Ser138Phe (c.413C>T) in the general population?

BPIFB2 p.Ser138Phe (c.413C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPIFB2 p.Ser138Phe (c.413C>T)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

BPIFB2 p.Ser138Phe

c.413C>T · VCV3992470

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -9.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76	GERP -3.3
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.62 · regional, not allelic
Overall
CADD	0.072	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BPIFB2
Protein: p.Ser138Phe
Coding: c.413C>T
MANE Select: NM_025227
Type: single nucleotide variant
Location: chr20:33013914 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.04
Residue 138: a disulfide bond

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

Similar variants

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
BPIFB2 p.Ala63Glu 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-ser138phe (accessed [today's date]).

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