Is BDP1 p.Val704Ala (c.2111T>C) pathogenic?

BDP1 p.Val704Ala (c.2111T>C) is classified Uncertain significance in BDP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.1683); Ultra-rare (popmax 0.0259%, nfe).

How common is BDP1 p.Val704Ala (c.2111T>C) in the general population?

BDP1 p.Val704Ala (c.2111T>C) is ultra-rare (popmax 0.0259%, nfe) (gnomAD).

What do computational predictors say about BDP1 p.Val704Ala (c.2111T>C)?

AlphaMissense predicts likely benign (score 0.1683) — an in-silico prediction, not a clinical call.

BDP1 p.Val704Ala

c.2111T>C · VCV3824107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1683 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0259%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1683	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.72	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 2.7
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	4.578	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 0.0259% European (non-Finnish) · 306/1,179,992 alleles

Filtering AF 0.0235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0226%

Overall 0.02% 322/1,613,930 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0259%	3,856
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-American	0.00534%	18,734
Admixed American	0.00167%	59,990
Finnishnot grpmax-eligible	0.00156%	64,018
South Asian	0.0011%	91,068

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.Val704Ala
Coding: c.2111T>C
MANE Select: NM_018429
Type: single nucleotide variant
Location: chr5:71502661 (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-val704ala (accessed [today's date]).

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