Is BDP1 p.Pro2245Ala (c.6733C>G) pathogenic?

BDP1 p.Pro2245Ala (c.6733C>G) is classified Uncertain significance in BDP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-13). AlphaMissense: likely benign (0.0904); Very rare (popmax 0.00449%, nfe).

How common is BDP1 p.Pro2245Ala (c.6733C>G) in the general population?

BDP1 p.Pro2245Ala (c.6733C>G) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about BDP1 p.Pro2245Ala (c.6733C>G)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

BDP1 p.Pro2245Ala

c.6733C>G · rs367642215 · VCV1049191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -6.39	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 1.2	GERP 1.2, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 23 kb · p 0.89 · regional, not allelic
Overall
CADD	10.92	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% European (non-Finnish) · 53/1,179,720 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00353% 57/1,612,784 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,259
Remaining individualsnot grpmax-eligible	0.0032%	31,228
African / African-American	0.00134%	74,656
South Asian	0.0011%	90,902

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: BDP1
Protein: p.Pro2245Ala
Coding: c.6733C>G
MANE Select: NM_018429
dbSNP: rs367642215
Type: single nucleotide variant
Location: chr5:71545208 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 37.23 · 13 PDB

Full BDP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/bdp1-p-pro2245ala (accessed [today's date]).

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