Is BDP1 p.Pro1963Leu (c.5888C>T) pathogenic?

BDP1 p.Pro1963Leu (c.5888C>T) is classified Uncertain significance in BDP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: likely benign (0.0998); Very rare (popmax 0.00551%, sas); Associated with hearing loss, autosomal recessive 112.

What condition is associated with BDP1 p.Pro1963Leu (c.5888C>T)?

BDP1 p.Pro1963Leu (c.5888C>T) is associated with hearing loss, autosomal recessive 112 (ClinVar).

How common is BDP1 p.Pro1963Leu (c.5888C>T) in the general population?

BDP1 p.Pro1963Leu (c.5888C>T) is very rare (popmax 0.00551%, sas) (gnomAD).

What do computational predictors say about BDP1 p.Pro1963Leu (c.5888C>T)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

BDP1 p.Pro1963Leu

c.5888C>T · rs549534181 · VCV2439509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hearing loss, autosomal recessive 112

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.96 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP 1.2, phastCons 0.011
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	18.52	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 0.00551% South Asian · 5/90,726 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000496% 8/1,612,536 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00551%	18,145
Remaining individualsnot grpmax-eligible	0.0016%	62,430
European (non-Finnish)	0.00017%	589,668

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.Pro1963Leu
Coding: c.5888C>T
MANE Select: NM_018429
dbSNP: rs549534181
Type: single nucleotide variant
Location: chr5:71532423 (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

Disease context

hearing loss, autosomal recessive 112 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BDP1 p.Pro1963= Benign ★★ same residue
BDP1 p.Arg935Ile Uncertain significance ★★ ⚠ same condition
BDP1 c.2373-15C>T Benign/Likely benign ★★ same condition
BDP1 c.4060-77G>A Benign ★★ same condition
BDP1 c.5893-36G>A Benign ★★ same condition
BDP1 p.Asp38Glu Benign ★★ same condition
BDP1 p.Gly1180Ser Benign ★★ same condition
BDP1 p.Ile1264Met Benign ★★ same condition

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-pro1963leu (accessed [today's date]).

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