Is ACVR2B p.Ser484= (c.1452G>A) pathogenic?

ACVR2B p.Ser484= (c.1452G>A) is classified Benign/Likely benign in ACVR2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-25). Rare (popmax 0.152%, eas); Associated with heterotaxy, visceral, 4, autosomal.

What condition is associated with ACVR2B p.Ser484= (c.1452G>A)?

ACVR2B p.Ser484= (c.1452G>A) is associated with heterotaxy, visceral, 4, autosomal (ClinVar).

How common is ACVR2B p.Ser484= (c.1452G>A) in the general population?

ACVR2B p.Ser484= (c.1452G>A) is rare (popmax 0.152%, eas) (gnomAD).

ACVR2B p.Ser484=

c.1452G>A · rs56280856 · VCV344919

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.152%, eas)

Conditions

heterotaxy, visceral, 4, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	donor gain · deltas
Pangolin	Δ0.38	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -3.1	GERP -4.1
Overall
CADD	14.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.152% East Asian · 68/44,872 alleles

Filtering AF 0.123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.0088% 142/1,614,004 alleles · rare exomes 116/1,461,884 · genomes 26/152,120 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.152%	660
Remaining individualsnot grpmax-eligible	0.0656%	1,525
African / African-American	0.0294%	3,407
Admixed American	0.00667%	15,002
European (non-Finnish)	0.000593%	168,573

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.Ser484=
Coding: c.1452G>A
MANE Select: NM_001106
dbSNP: rs56280856
Type: single nucleotide variant
Location: chr3:38483245 (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.Ser484Leu 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-ser484 (accessed [today's date]).

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