Is BDP1 p.Ala1985Val (c.5954C>T) pathogenic?

BDP1 p.Ala1985Val (c.5954C>T) is classified Uncertain significance in BDP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.8496); Very rare (popmax 8.49e-05%, nfe).

How common is BDP1 p.Ala1985Val (c.5954C>T) in the general population?

BDP1 p.Ala1985Val (c.5954C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about BDP1 p.Ala1985Val (c.5954C>T)?

AlphaMissense predicts likely pathogenic (score 0.8496) — an in-silico prediction, not a clinical call.

BDP1 p.Ala1985Val

c.5954C>T · VCV4645677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8496 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8496	likely pathogenic · top 5% in BDP1
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 4.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	25.9	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 8.49e-05% European (non-Finnish) · 1/1,178,504 alleles

Overall 6.85e-05% 1/1,460,026 alleles · very rare

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.Ala1985Val
Coding: c.5954C>T
MANE Select: NM_018429
Type: single nucleotide variant
Location: chr5:71539581 (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

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-ala1985val (accessed [today's date]).

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