Is ACVR2B p.Asn486= (c.1458C>T) pathogenic?

ACVR2B p.Asn486= (c.1458C>T) is classified Benign in ACVR2B (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Common (popmax 56.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with heterotaxy, visceral, 4, autosomal.

What condition is associated with ACVR2B p.Asn486= (c.1458C>T)?

ACVR2B p.Asn486= (c.1458C>T) is associated with heterotaxy, visceral, 4, autosomal (ClinVar).

ACVR2B p.Asn486=

Q: How common is ACVR2B p.Asn486= (c.1458C>T) in the general population?

ACVR2B p.Asn486= (c.1458C>T) is common (popmax 56.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1458C>T · rs1046048 · VCV257467

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 56.8%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

heterotaxy, visceral, 4, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2
Overall
CADD	9.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 56.8% European (non-Finnish) · 670,023/1,179,852 alleles

Filtering AF 56.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 56.6%

Overall 52.6% 848,200/1,613,586 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	56.8%	2
Finnishnot grpmax-eligible	53.9%	2
South Asian	52%	2
Remaining individualsnot grpmax-eligible	50%	2
Ashkenazi Jewishnot grpmax-eligible	49.3%	2
Middle Eastern	47.7%	2
Amishnot grpmax-eligible	46.6%	2
Admixed American	35.1%	3
East Asian	30.1%	3
African / African-American	17%	6

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.Asn486=
Coding: c.1458C>T
MANE Select: NM_001106
dbSNP: rs1046048
Type: single nucleotide variant
Location: chr3:38483251 (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

Disease context

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

Similar variants

ACVR2B p.Asn486Ser 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.Arg482Gln 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-asn486 (accessed [today's date]).

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