Is ACVR2B p.Cys49= (c.147C>T) pathogenic?

ACVR2B p.Cys49= (c.147C>T) is classified Benign/Likely benign in ACVR2B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-12). Low-frequency (popmax 1.1%, sas); Associated with heterotaxy, visceral, 4, autosomal.

What condition is associated with ACVR2B p.Cys49= (c.147C>T)?

ACVR2B p.Cys49= (c.147C>T) is associated with heterotaxy, visceral, 4, autosomal (ClinVar).

How common is ACVR2B p.Cys49= (c.147C>T) in the general population?

ACVR2B p.Cys49= (c.147C>T) is low-frequency (popmax 1.1%, sas) (gnomAD).

ACVR2B p.Cys49=

c.147C>T · rs201686292 · VCV344912

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, sas)

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 -6.2	GERP -4.1
Overall
CADD	8.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.1% South Asian · 1,001/91,084 alleles

Filtering AF 1.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.02%

Overall 0.0693% 1,119/1,614,150 alleles · low-frequency exomes 1,054/1,461,854 · genomes 65/152,296 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.1%	91
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Middle Eastern	0.0825%	1,212
Admixed American	0.0133%	7,504
African / African-American	0.00533%	18,760
East Asian	0.00446%	22,432
European (non-Finnish)	0.00373%	26,818
Finnishnot grpmax-eligible	0.00156%	64,026

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.Cys49=
Coding: c.147C>T
MANE Select: NM_001106
dbSNP: rs201686292
Type: single nucleotide variant
Location: chr3:38477381 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 9 PDB
Residue 49: a disulfide bond; a β-strand

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 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
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-cys49 (accessed [today's date]).

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