Is BMP8B p.Arg263Trp (c.787C>T) pathogenic?

BMP8B p.Arg263Trp (c.787C>T) is classified Uncertain significance in BMP8B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.2217); Very rare (popmax 0.00549%, sas).

How common is BMP8B p.Arg263Trp (c.787C>T) in the general population?

BMP8B p.Arg263Trp (c.787C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about BMP8B p.Arg263Trp (c.787C>T)?

AlphaMissense predicts likely benign (score 0.2217) — an in-silico prediction, not a clinical call.

BMP8B p.Arg263Trp

c.787C>T · VCV4646243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2217 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2217	likely benign
REVEL	0.402	indeterminate
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP -0.5, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 129 bp · p 1.7e-15 · regional, not allelic
Overall
CADD	27.0	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 0.00549% South Asian · 5/91,076 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00093% 15/1,613,436 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,215
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.000678%	147,471

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: BMP8B
Protein: p.Arg263Trp
Coding: c.787C>T
MANE Select: NM_001720
Type: single nucleotide variant
Location: chr1:39764704 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.96

Full BMP8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP8B p.Arg263Gln Uncertain significance ★ ⚠ same residue
BMP8B c.1059+579A>G Benign/Likely benign ★★ same type
BMP8B p.Leu118= Likely benign ★★ same type
BMP8B p.Ser276Thr Benign ★★ same type
BMP8B p.Ser326= Benign/Likely benign ★★ same type
BMP8B c.673+3659A>G Conflicting classifications of pathogenicity ★ ⚠ same type
BMP8B p.Ala344Val Uncertain significance ★ ⚠ same type
BMP8B p.Ala348Thr 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/bmp8b-p-arg263trp (accessed [today's date]).

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