Is ACVR2B p.Arg482Trp (c.1444C>T) pathogenic?

ACVR2B p.Arg482Trp (c.1444C>T) is classified Benign/Likely benign in ACVR2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-30). AlphaMissense: likely benign (0.2291); Ultra-rare (popmax 0.0307%, afr); Associated with heterotaxy, visceral, 4, autosomal.

What condition is associated with ACVR2B p.Arg482Trp (c.1444C>T)?

ACVR2B p.Arg482Trp (c.1444C>T) is associated with heterotaxy, visceral, 4, autosomal (ClinVar).

How common is ACVR2B p.Arg482Trp (c.1444C>T) in the general population?

ACVR2B p.Arg482Trp (c.1444C>T) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about ACVR2B p.Arg482Trp (c.1444C>T)?

AlphaMissense predicts likely benign (score 0.2291) — an in-silico prediction, not a clinical call.

ACVR2B p.Arg482Trp

c.1444C>T · rs144370188 · VCV344918

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2291 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

heterotaxy, visceral, 4, autosomal

Computational evidence

Protein change
AlphaMissense	0.2291	likely benign
REVEL	0.521	indeterminate
SaProt	LLR -9.91	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 4.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 4,811 bp · p 9.8e-17 · regional, not allelic
Overall
CADD	25.9	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 0.0307% African / African-American · 23/74,974 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.028% 452/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.06%	95
Remaining individualsnot grpmax-eligible	0.072%	1,389
African / African-Americangrpmax	0.0307%	3,260
European (non-Finnish)	0.00585%	17,102
East Asian	0.00446%	22,435

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACVR2B
Protein: p.Arg482Trp
Coding: c.1444C>T
MANE Select: NM_001106
dbSNP: rs144370188
Type: single nucleotide variant
Location: chr3:38483237 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 9 PDB
Residue 482: an α-helix

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

Disease context

heterotaxy, visceral, 4, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACVR2B p.Arg482Gln Uncertain significance ★★ ⚠ same residue
ACVR2B c.*4984T>C Uncertain significance ★★ same condition
ACVR2B c.*9473T>C Uncertain significance ★★ same condition
ACVR2B p.Arg161Trp Uncertain significance ★★ ⚠ same condition
ACVR2B p.Arg163His Uncertain significance ★★ ⚠ same condition
ACVR2B p.Arg21His Uncertain significance ★★ ⚠ same condition
ACVR2B p.Arg309His Uncertain significance ★★ ⚠ same condition
ACVR2B p.Gln246His Uncertain significance ★★ ⚠ same condition

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-arg482trp (accessed [today's date]).

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