Is BDP1 p.Ala1685Pro (c.5053G>C) pathogenic?

BDP1 p.Ala1685Pro (c.5053G>C) is classified Likely benign in BDP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-26). AlphaMissense: likely benign (0.1695); Ultra-rare (popmax 0.0183%, amr).

How common is BDP1 p.Ala1685Pro (c.5053G>C) in the general population?

BDP1 p.Ala1685Pro (c.5053G>C) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about BDP1 p.Ala1685Pro (c.5053G>C)?

AlphaMissense predicts likely benign (score 0.1695) — an in-silico prediction, not a clinical call.

BDP1 p.Ala1685Pro

c.5053G>C · rs200843292 · VCV1315765

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1695 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1695	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -2.02	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 0.16	GERP -3.2, phastCons 0.002
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	7.827	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/59,994 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.015% 242/1,613,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.466%	214
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed Americangrpmax	0.0183%	5,454
European (non-Finnish)	0.00619%	16,164

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala1685Pro
Coding: c.5053G>C
MANE Select: NM_018429
dbSNP: rs200843292
Type: single nucleotide variant
Location: chr5:71522350 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 37.23 · 13 PDB
Residue 1685: the 'disordered' region

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

Similar variants

BDP1 p.Arg880Gly Uncertain significance ★★ ⚠ same type
BDP1 p.Arg935Ile Uncertain significance ★★ ⚠ same type
BDP1 p.Asp1875Asn Uncertain significance ★★ ⚠ same type
BDP1 p.Glu1139Val Uncertain significance ★★ ⚠ same type
BDP1 p.Ile1035Met Uncertain significance ★★ ⚠ same type
BDP1 p.Lys1304Glu Uncertain significance ★★ ⚠ same type
BDP1 p.Lys354Glu Uncertain significance ★★ ⚠ same type
BDP1 p.Pro1432Leu Uncertain significance ★★ ⚠ 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/bdp1-p-ala1685pro (accessed [today's date]).

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