Is ACVR2B p.Ala140= (c.420C>T) pathogenic?

ACVR2B p.Ala140= (c.420C>T) is classified Likely benign in ACVR2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-20). Ultra-rare (popmax 0.0172%, mid); Associated with heterotaxy, visceral, 4, autosomal.

What condition is associated with ACVR2B p.Ala140= (c.420C>T)?

ACVR2B p.Ala140= (c.420C>T) is associated with heterotaxy, visceral, 4, autosomal (ClinVar).

How common is ACVR2B p.Ala140= (c.420C>T) in the general population?

ACVR2B p.Ala140= (c.420C>T) is ultra-rare (popmax 0.0172%, mid) (gnomAD).

ACVR2B p.Ala140=

c.420C>T · rs2471257527 · VCV2740110

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, mid)

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 0.65	GERP 1.6, phastCons 1
Overall
CADD	12.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0172% Middle Eastern · 1/5,804 alleles

Overall 6.84e-05% 1/1,461,498 alleles · ultra-rare

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.Ala140=
Coding: c.420C>T
MANE Select: NM_001106
dbSNP: rs2471257527
Type: single nucleotide variant
Location: chr3:38478190 (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 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-ala140 (accessed [today's date]).

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