Is BPI p.Arg86Cys (c.256C>T) pathogenic?

BPI p.Arg86Cys (c.256C>T) is classified Benign in BPI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-26). AlphaMissense: likely benign (0.1567); Low-frequency (popmax 1.66%, amr).

How common is BPI p.Arg86Cys (c.256C>T) in the general population?

BPI p.Arg86Cys (c.256C>T) is low-frequency (popmax 1.66%, amr) (gnomAD).

What do computational predictors say about BPI p.Arg86Cys (c.256C>T)?

AlphaMissense predicts likely benign (score 0.1567) — an in-silico prediction, not a clinical call.

BPI p.Arg86Cys

c.256C>T · rs5743500 · VCV777548

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1567 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.66%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1567	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -4
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic
Overall
CADD	19.76	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 R90C vs ClinVar R86C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.66% Admixed American · 999/60,028 alleles

Filtering AF 1.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.54%

Overall 0.0975% 1,573/1,614,134 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	1.66%	60
East Asian	0.537%	186
Remaining individualsnot grpmax-eligible	0.064%	1,563
South Asian	0.034%	2,938
European (non-Finnish)	0.0206%	4,856
African / African-American	0.0147%	6,821
Finnishnot grpmax-eligible	0.0125%	8,003

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.Arg86Cys
Coding: c.256C>T
MANE Select: NM_001725
dbSNP: rs5743500
Type: single nucleotide variant
Location: chr20:38308940 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.70 · 2 PDB
Residue 86: the 'n-terminal barrel' 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.Glu136Gln Benign ★★ same type
BPI p.Glu212Lys 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-arg86cys (accessed [today's date]).

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