Is ACVR2B p.Pro128Arg (c.383C>G) pathogenic?

ACVR2B p.Pro128Arg (c.383C>G) is classified Uncertain significance in ACVR2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely benign (0.0972); Absent from gnomAD v4.1.

How common is ACVR2B p.Pro128Arg (c.383C>G) in the general population?

ACVR2B p.Pro128Arg (c.383C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACVR2B p.Pro128Arg (c.383C>G)?

AlphaMissense predicts likely benign (score 0.0972) — an in-silico prediction, not a clinical call.

ACVR2B p.Pro128Arg

c.383C>G · rs749007843 · VCV2318870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0972 · 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	0.0972	likely benign
REVEL	0.394	indeterminate
SaProt	LLR -9.02	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 0.65, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 837 bp · p 7.9e-06 · regional, not allelic
Overall
CADD	23.1	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: ACVR2B
Protein: p.Pro128Arg
Coding: c.383C>G
MANE Select: NM_001106
dbSNP: rs749007843
Type: single nucleotide variant
Location: chr3:38478153 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 9 PDB

Full ACVR2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACVR2B c.*4984T>C Uncertain significance ★★ same type
ACVR2B c.*9473T>C Uncertain significance ★★ same type
ACVR2B p.Arg161Trp Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg163His Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg21His Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg309His Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg482Gln Uncertain significance ★★ ⚠ same type
ACVR2B p.Gln246His 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/acvr2b-p-pro128arg (accessed [today's date]).

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