Is BPIFA2 p.Gln3Pro (c.8A>C) pathogenic?

BPIFA2 p.Gln3Pro (c.8A>C) is classified Uncertain significance in BPIFA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.0872); Absent from gnomAD v4.1.

How common is BPIFA2 p.Gln3Pro (c.8A>C) in the general population?

BPIFA2 p.Gln3Pro (c.8A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPIFA2 p.Gln3Pro (c.8A>C)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

BPIFA2 p.Gln3Pro

c.8A>C · VCV3992439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.14	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 0.57	GERP -2.1, phastCons 0.002
Regional constraint	o/e 1.01	unconstrained · MANE · 11 kb · p 0.91 · regional, not allelic
Overall
CADD	22.3	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.

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: BPIFA2
Protein: p.Gln3Pro
Coding: c.8A>C
MANE Select: NM_080574
Type: single nucleotide variant
Location: chr20:33169153 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.37

Full BPIFA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BPIFA2 p.Gly101= Benign ★★ same type
BPIFA2 p.Ala131Val Uncertain significance ★ ⚠ same type
BPIFA2 p.Ala155Pro Uncertain significance ★ ⚠ same type
BPIFA2 p.Ala155Thr Uncertain significance ★ ⚠ same type
BPIFA2 p.Asp118Asn Uncertain significance ★ ⚠ same type
BPIFA2 p.Asp187Glu Uncertain significance ★ ⚠ same type
BPIFA2 p.Asp28Glu Uncertain significance ★ ⚠ same type
BPIFA2 p.Gln66Arg 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/bpifa2-p-gln3pro (accessed [today's date]).

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