Is BDP1 p.Arg400Trp (c.1198C>T) pathogenic?

BDP1 p.Arg400Trp (c.1198C>T) is classified Uncertain significance in BDP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-02). AlphaMissense: likely benign (0.2287); Ultra-rare (popmax 0.0208%, mid).

How common is BDP1 p.Arg400Trp (c.1198C>T) in the general population?

BDP1 p.Arg400Trp (c.1198C>T) is ultra-rare (popmax 0.0208%, mid) (gnomAD).

What do computational predictors say about BDP1 p.Arg400Trp (c.1198C>T)?

AlphaMissense predicts likely benign (score 0.2287) — an in-silico prediction, not a clinical call.

BDP1 p.Arg400Trp

c.1198C>T · rs202072250 · VCV3133613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2287 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2287	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -9.81	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 1.4	GERP 3.3, phastCons 0.9
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	24.8	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 0.0208% Middle Eastern · 1/4,810 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00269% 41/1,522,262 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0208%	4,810
African / African-American	0.00582%	17,191
Remaining individualsnot grpmax-eligible	0.00516%	19,395
Ashkenazi Jewishnot grpmax-eligible	0.00383%	26,092
Admixed American	0.00266%	37,562
European (non-Finnish)	0.00261%	38,267
East Asian	0.00254%	39,332

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.Arg400Trp
Coding: c.1198C>T
MANE Select: NM_018429
dbSNP: rs202072250
Type: single nucleotide variant
Location: chr5:71486612 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 37.23 · 13 PDB
Residue 400: the 'required for phosphorylation by csnk2a1' region; the 'disordered' region

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

Similar variants

BDP1 p.Arg400Gln Uncertain significance ★ ⚠ same residue
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

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-arg400trp (accessed [today's date]).

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