Is BPI p.Phe473Ile (c.1417T>A) pathogenic?

BPI p.Phe473Ile (c.1417T>A) is classified Uncertain significance in BPI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely pathogenic (0.5948); Ultra-rare (popmax 0.0458%, eas).

How common is BPI p.Phe473Ile (c.1417T>A) in the general population?

BPI p.Phe473Ile (c.1417T>A) is ultra-rare (popmax 0.0458%, eas) (gnomAD).

What do computational predictors say about BPI p.Phe473Ile (c.1417T>A)?

AlphaMissense predicts likely pathogenic (score 0.5948) — an in-silico prediction, not a clinical call.

BPI p.Phe473Ile

c.1417T>A · rs199545210 · VCV3134801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5948 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5948	likely pathogenic
REVEL	0.211	benign-leaning
SaProt	LLR -11.30	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 2.7	GERP -0.11, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic
Overall
CADD	23.3	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 F477I vs ClinVar F473I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0458% East Asian · 20/43,686 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0253%

Overall 0.00131% 21/1,601,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0458%	2,184
Remaining individualsnot grpmax-eligible	0.00161%	62,034

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.Phe473Ile
Coding: c.1417T>A
MANE Select: NM_001725
dbSNP: rs199545210
Type: single nucleotide variant
Location: chr20:38337149 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.70 · 2 PDB
Residue 473: the 'central sheet, part 3' region; a β-strand

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-phe473ile (accessed [today's date]).

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