Is BPI p.Ala192Val (c.575C>T) pathogenic?

BPI p.Ala192Val (c.575C>T) is classified Benign in BPI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-28). AlphaMissense: likely benign (0.1064); Common (popmax 11.4%, sas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BPI p.Ala192Val (c.575C>T)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

BPI p.Ala192Val

Q: How common is BPI p.Ala192Val (c.575C>T) in the general population?

BPI p.Ala192Val (c.575C>T) is common (popmax 11.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.575C>T · rs5743509 · VCV402433

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.4%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.78	GERP -4
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic
Overall
CADD	9.395	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 A196V vs ClinVar A192V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.4% South Asian · 10,395/91,026 alleles

Filtering AF 11.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.2%

Overall 5.59% 90,164/1,613,722 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	11.4%	9
Middle Eastern	8.79%	11
Ashkenazi Jewishnot grpmax-eligible	6.05%	17
Remaining individualsnot grpmax-eligible	5.72%	17
European (non-Finnish)	5.7%	18
East Asian	3.78%	26
Admixed American	2.86%	35
Finnishnot grpmax-eligible	2.64%	38
African / African-American	2.01%	50

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.Ala192Val
Coding: c.575C>T
MANE Select: NM_001725
dbSNP: rs5743509
Type: single nucleotide variant
Location: chr20:38311912 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.70 · 2 PDB
Residue 192: the 'n-terminal barrel' region; an α-helix; a disulfide bond

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.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
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-ala192val (accessed [today's date]).

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