Is BPIFA3 p.Pro244Ala (c.730C>G) pathogenic?

BPIFA3 p.Pro244Ala (c.730C>G) is classified Uncertain significance in BPIFA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0573); Absent from gnomAD v4.1.

How common is BPIFA3 p.Pro244Ala (c.730C>G) in the general population?

BPIFA3 p.Pro244Ala (c.730C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPIFA3 p.Pro244Ala (c.730C>G)?

AlphaMissense predicts likely benign (score 0.0573) — an in-silico prediction, not a clinical call.

BPIFA3 p.Pro244Ala

c.730C>G · VCV4214878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0573 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0573	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.98	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 -1.4
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.51 · regional, not allelic
Overall
CADD	5.083	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: BPIFA3
Protein: p.Pro244Ala
Coding: c.730C>G
MANE Select: NM_178466
Type: single nucleotide variant
Location: chr20:33227582 (GRCh38)
Gene constraint: LOEUF 1.511 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.36
Residue 244: the 'disordered' region

Full BPIFA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BPIFA3 p.Pro244Ser Uncertain significance ★ ⚠ same residue
BPIFA3 p.Ala140Val Uncertain significance ★ ⚠ same type
BPIFA3 p.Ala20Ser Uncertain significance ★ ⚠ same type
BPIFA3 p.Ala53Thr Uncertain significance ★ ⚠ same type
BPIFA3 p.Ala73Thr Uncertain significance ★ ⚠ same type
BPIFA3 p.Asn67Ser Uncertain significance ★ ⚠ same type
BPIFA3 p.Asp132His Uncertain significance ★ ⚠ same type
BPIFA3 p.Gln46Pro 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/bpifa3-p-pro244ala (accessed [today's date]).

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