Is BPI p.Ser208Phe (c.623C>T) pathogenic?

BPI p.Ser208Phe (c.623C>T) is classified Uncertain significance in BPI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-20). AlphaMissense: likely benign (0.2026); Very rare (popmax 0.00534%, afr).

How common is BPI p.Ser208Phe (c.623C>T) in the general population?

BPI p.Ser208Phe (c.623C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about BPI p.Ser208Phe (c.623C>T)?

AlphaMissense predicts likely benign (score 0.2026) — an in-silico prediction, not a clinical call.

BPI p.Ser208Phe

c.623C>T · rs372552649 · VCV2466089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2026	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP 2.5, phastCons 0.008
Regional constraint	o/e 1.07	unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S212F vs ClinVar S208F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,916 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,613,780 alleles · very rare exomes 2/1,461,588 · genomes 3/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,729
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Ser208Phe
Coding: c.623C>T
MANE Select: NM_001725
dbSNP: rs372552649
Type: single nucleotide variant
Location: chr20:38318435 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.70 · 2 PDB
Residue 212 UniProt numbering: the 'n-terminal barrel' region; an α-helix

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-ser208phe (accessed [today's date]).

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