Is ACVR2B p.Met1Val (c.1A>G) pathogenic?

ACVR2B p.Met1Val (c.1A>G) is classified Uncertain significance in ACVR2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). No allele count reported in gnomAD v4.1 (AN 1,296,534); Associated with heterotaxy, visceral, 4, autosomal.

What condition is associated with ACVR2B p.Met1Val (c.1A>G)?

ACVR2B p.Met1Val (c.1A>G) is associated with heterotaxy, visceral, 4, autosomal (ClinVar).

How common is ACVR2B p.Met1Val (c.1A>G) in the general population?

ACVR2B p.Met1Val (c.1A>G) is no allele count reported in gnomAD v4.1 (AN 1,296,534) (gnomAD).

ACVR2B p.Met1Val

c.1A>G · rs1559642966 · VCV579672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,296,534)

Conditions

heterotaxy, visceral, 4, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.434	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 10	GERP -0.3, phastCons 1
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,296,534). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACVR2B
Protein: p.Met1Val
Coding: c.1A>G
dbSNP: rs1559642966
Type: single nucleotide variant
Location: chr3:38454323 (GRCh38)

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

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-met1val (accessed [today's date]).

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