Is BMPR1B p.Ser48Arg (c.144C>G) pathogenic?

BMPR1B p.Ser48Arg (c.144C>G) is classified Uncertain significance in BMPR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.1542); Absent from gnomAD v4.1.

How common is BMPR1B p.Ser48Arg (c.144C>G) in the general population?

BMPR1B p.Ser48Arg (c.144C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPR1B p.Ser48Arg (c.144C>G)?

AlphaMissense predicts likely benign (score 0.1542) — an in-silico prediction, not a clinical call.

BMPR1B p.Ser48Arg

c.144C>G · VCV4967870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1542 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1542	likely benign
REVEL	0.567	indeterminate
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 10 kb · p 5.8e-08 · regional, not allelic
Overall
CADD	16.59	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMPR1B
Protein: p.Ser48Arg
Coding: c.144C>G
MANE Select: NM_001203
Type: single nucleotide variant
Location: chr4:95114720 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 48: a disulfide bond

Full BMPR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMPR1B c.585+1G>C Likely pathogenic ★★ same type
BMPR1B p.Arg486Trp Pathogenic ★★ same type
BMPR1B c.*828T>G Uncertain significance ★★ same type
BMPR1B c.*83C>G Uncertain significance ★★ same type
BMPR1B p.Arg214His Uncertain significance ★★ ⚠ same type
BMPR1B p.Arg26Pro Uncertain significance ★★ ⚠ same type
BMPR1B p.Arg412Gly Uncertain significance ★★ ⚠ same type
BMPR1B p.Arg91Ile 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/bmpr1b-p-ser48arg (accessed [today's date]).

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