Is ACVR2B c.1344+287C>G pathogenic?

ACVR2B c.1344+287C>G is classified Benign in ACVR2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). Common (popmax 8.94%, afr) — too common for a highly-penetrant pathogenic allele.

ACVR2B c.1344+287C>G

Q: How common is ACVR2B c.1344+287C>G in the general population?

ACVR2B c.1344+287C>G is common (popmax 8.94%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs78041404 · VCV1295055

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 8.94%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +287	deep intronic (+287 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP 1.3
Overall
CADD	2.658	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.94% African / African-American · 3,710/41,500 alleles

Filtering AF 8.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.6%

Overall 2.62% 3,993/152,182 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.94%	11
Remaining individualsnot grpmax-eligible	2.36%	42
Admixed American	1.08%	93
Ashkenazi Jewishnot grpmax-eligible	0.893%	112
Middle Eastern	0.34%	294
European (non-Finnish)	0.05%	2,000
South Asian	0.0415%	2,410

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
Coding: c.1344+287C>G
MANE Select: NM_001106
dbSNP: rs78041404
Type: single nucleotide variant
Location: chr3:38482847 (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

Similar variants

ACVR2B c.*4984T>C Uncertain significance ★★ same type
ACVR2B c.*9473T>C Uncertain significance ★★ same type
ACVR2B p.Arg161Trp Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg163His Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg21His Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg309His Uncertain significance ★★ ⚠ same type
ACVR2B p.Arg482Gln Uncertain significance ★★ ⚠ same type
ACVR2B p.Gln246His Uncertain significance ★★ ⚠ same type

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-c-1344-plus-287c-g (accessed [today's date]).

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