Is BPI p.Glu136Gln (c.406G>C) pathogenic?

BPI p.Glu136Gln (c.406G>C) is classified Benign in BPI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-15). AlphaMissense: likely benign (0.0993); Low-frequency (popmax 1.43%, afr).

How common is BPI p.Glu136Gln (c.406G>C) in the general population?

BPI p.Glu136Gln (c.406G>C) is low-frequency (popmax 1.43%, afr) (gnomAD).

What do computational predictors say about BPI p.Glu136Gln (c.406G>C)?

AlphaMissense predicts likely benign (score 0.0993) — an in-silico prediction, not a clinical call.

BPI p.Glu136Gln

c.406G>C · rs5743506 · VCV786367

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0993 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.43%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0993	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.31	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 0.26	GERP -2.1
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic
Overall
CADD	1.352	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 E140Q vs ClinVar E136Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.43% African / African-American · 1,070/75,030 alleles

Filtering AF 1.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.33%

Overall 0.0798% 1,288/1,614,100 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.43%	70
Middle Eastern	0.363%	276
Remaining individualsnot grpmax-eligible	0.12%	833
Admixed American	0.12%	834
South Asian	0.00879%	11,382
European (non-Finnish)	0.00347%	28,780

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.Glu136Gln
Coding: c.406G>C
MANE Select: NM_001725
dbSNP: rs5743506
Type: single nucleotide variant
Location: chr20:38310522 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.70 · 2 PDB
Residue 136: 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.Arg86Cys 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-glu136gln (accessed [today's date]).

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