Is BPI p.Ala230Pro (c.688G>C) pathogenic?

BPI p.Ala230Pro (c.688G>C) is classified Uncertain significance in BPI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.9293); Very rare (popmax 6.84e-05%).

How common is BPI p.Ala230Pro (c.688G>C) in the general population?

BPI p.Ala230Pro (c.688G>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about BPI p.Ala230Pro (c.688G>C)?

AlphaMissense predicts likely pathogenic (score 0.9293) — an in-silico prediction, not a clinical call.

BPI p.Ala230Pro

c.688G>C · rs746839185 · VCV2614546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9293	likely pathogenic · top 1% in BPI
REVEL	0.196	benign-leaning
SaProt	LLR -13.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A234P vs ClinVar A230P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,838 alleles · very rare

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: BPI
Protein: p.Ala230Pro
Coding: c.688G>C
MANE Select: NM_001725
dbSNP: rs746839185
Type: single nucleotide variant
Location: chr20:38320206 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.70 · 2 PDB
Residue 230: the 'central sheet, part 2' region

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

Similar variants

BPI c.664+7G>T Benign ★★ same type
BPI p.Ala12Val Benign ★★ same type
BPI p.Ala192Val Benign ★★ same type
BPI p.Ala333Thr Likely benign ★★ same type
BPI p.Ala8Thr Benign ★★ same type
BPI p.Ala8Val Benign ★★ same type
BPI p.Arg86Cys Benign ★★ ⚠ same type
BPI p.Glu136Gln Benign ★★ 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/bpi-p-ala230pro (accessed [today's date]).

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