Is BDP1 p.Val1546Phe (c.4636G>T) pathogenic?

BDP1 p.Val1546Phe (c.4636G>T) is classified Benign/Likely benign in BDP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-23). AlphaMissense: likely benign (0.1458); Low-frequency (popmax 2.03%, afr).

How common is BDP1 p.Val1546Phe (c.4636G>T) in the general population?

BDP1 p.Val1546Phe (c.4636G>T) is low-frequency (popmax 2.03%, afr) (gnomAD).

What do computational predictors say about BDP1 p.Val1546Phe (c.4636G>T)?

AlphaMissense predicts likely benign (score 0.1458) — an in-silico prediction, not a clinical call.

BDP1 p.Val1546Phe

c.4636G>T · rs34719355 · VCV1221682

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1458 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.03%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1458	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.56	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 -0.17	GERP -0.32
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	12.56	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 2.03% African / African-American · 1,494/73,736 alleles

Filtering AF 1.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.91%

Overall 0.104% 1,658/1,595,112 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.03%	49
Middle Eastern	0.233%	429
Remaining individualsnot grpmax-eligible	0.115%	871
Admixed American	0.0638%	1,568
South Asian	0.0116%	8,649
European (non-Finnish)	0.0029%	34,538

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.Val1546Phe
Coding: c.4636G>T
MANE Select: NM_018429
dbSNP: rs34719355
Type: single nucleotide variant
Location: chr5:71515109 (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.Val1546Ile 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-val1546phe (accessed [today's date]).

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