Is BDP1 p.Arg757Cys (c.2269C>T) pathogenic?

BDP1 p.Arg757Cys (c.2269C>T) is classified Benign in BDP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-05-09). AlphaMissense: likely benign (0.0582); Common (popmax 56.6%, amr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BDP1 p.Arg757Cys (c.2269C>T)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

BDP1 p.Arg757Cys

Q: How common is BDP1 p.Arg757Cys (c.2269C>T) in the general population?

BDP1 p.Arg757Cys (c.2269C>T) is common (popmax 56.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2269C>T · rs3761966 · VCV517819

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 56.6%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.04	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 -0.43	GERP -1.6
Regional constraint	o/e 0.99	unconstrained · MANE · 86 kb · p 0.66 · regional, not allelic
Overall
CADD	1.353	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 56.6% Admixed American · 33,913/59,904 alleles

Filtering AF 56.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.9%

Overall 34.1% 549,255/1,611,948 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	56.6%	2
East Asian	50.2%	2
Ashkenazi Jewishnot grpmax-eligible	41.1%	2
Middle Eastern	35.3%	3
Remaining individualsnot grpmax-eligible	34.2%	3
European (non-Finnish)	34.2%	3
Finnishnot grpmax-eligible	29%	3
South Asian	27.6%	4
Amishnot grpmax-eligible	17.9%	6
African / African-American	14.2%	7

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.Arg757Cys
Coding: c.2269C>T
MANE Select: NM_018429
dbSNP: rs3761966
Type: single nucleotide variant
Location: chr5:71504648 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 37.23 · 13 PDB
Residue 757: the 'disordered' region; a UniProt-annotated variant site (in)

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

Similar variants

BDP1 p.Arg757His Conflicting classifications of pathogenicity ★ ⚠ same residue
BDP1 p.Arg757Leu 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

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-arg757cys (accessed [today's date]).

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