Is BPI p.Ala8Val (c.23C>T) pathogenic?

BPI p.Ala8Val (c.23C>T) is classified Benign in BPI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-13). AlphaMissense: likely benign (0.0883); Low-frequency (popmax 1.14%, afr).

How common is BPI p.Ala8Val (c.23C>T) in the general population?

BPI p.Ala8Val (c.23C>T) is low-frequency (popmax 1.14%, afr) (gnomAD).

What do computational predictors say about BPI p.Ala8Val (c.23C>T)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

BPI p.Ala8Val

c.23C>T · rs5743498 · VCV788033

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.14%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.37	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 -4.9	GERP -3.6
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic
Overall
CADD	0.02	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 A12V vs ClinVar A8V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.14% African / African-American · 858/75,036 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.061% 984/1,614,166 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.14%	87
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.0267%	3,752
European (non-Finnish)	0.00525%	19,033
South Asian	0.0022%	45,544

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.Ala8Val
Coding: c.23C>T
MANE Select: NM_001725
dbSNP: rs5743498
Type: single nucleotide variant
Location: chr20:38304246 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.70 · 2 PDB

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

Similar variants

BPI p.Ala8Thr Benign ★★ same residue
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.Arg86Cys 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-ala8val (accessed [today's date]).

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