Is ACVR2B p.Glu260Asp (c.780G>C) pathogenic?

ACVR2B p.Glu260Asp (c.780G>C) is classified Uncertain significance in ACVR2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: ambiguous (0.4127); Absent from gnomAD v4.1.

How common is ACVR2B p.Glu260Asp (c.780G>C) in the general population?

ACVR2B p.Glu260Asp (c.780G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACVR2B p.Glu260Asp (c.780G>C)?

AlphaMissense predicts ambiguous (score 0.4127) — an in-silico prediction, not a clinical call.

ACVR2B p.Glu260Asp

c.780G>C · VCV3827110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4127 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4127	ambiguous
REVEL	0.216	benign-leaning
SaProt	LLR -11.34	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -1.4, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 4,811 bp · p 9.8e-17 · regional, not allelic
Overall
CADD	19.85	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

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.Glu260Asp
Coding: c.780G>C
MANE Select: NM_001106
Type: single nucleotide variant
Location: chr3:38479241 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 9 PDB
Residue 260: a β-strand; the protein kinase domain

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-glu260asp (accessed [today's date]).

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