Is ACVR1 p.Ser290= (c.870G>A) pathogenic?

ACVR1 p.Ser290= (c.870G>A) is classified Benign/Likely benign in ACVR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.02%, amr).

How common is ACVR1 p.Ser290= (c.870G>A) in the general population?

ACVR1 p.Ser290= (c.870G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

ACVR1 p.Ser290=

c.870G>A · rs548498262 · VCV713453

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

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 -8.6	GERP -5.5
Overall
CADD	5.806	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,022 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00403% 65/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed Americangrpmax	0.02%	5,002
East Asian	0.0178%	5,609
Finnishnot grpmax-eligible	0.0156%	6,400
African / African-American	0.00533%	18,755
South Asian	0.0011%	91,072
European (non-Finnish)	0.000678%	147,495

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACVR1
Protein: p.Ser290=
Coding: c.870G>A
MANE Select: NM_001111067
dbSNP: rs548498262
Type: single nucleotide variant
Location: chr2:157766117 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.70 · 85 PDB
Residue 290: the protein kinase domain

Full ACVR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACVR1 p.Arg206His Pathogenic ★★ same type
ACVR1 p.Gly328Glu Pathogenic/Likely pathogenic ★★ same type
ACVR1 p.Gly356Asp Pathogenic/Likely pathogenic ★★ same type
ACVR1 p.Ala134Thr Uncertain significance ★★ ⚠ same type
ACVR1 p.Arg147Gln Uncertain significance ★★ ⚠ same type
ACVR1 p.Arg160Ter Uncertain significance ★★ same type
ACVR1 p.Arg307Gln Uncertain significance ★★ ⚠ same type
ACVR1 p.Arg417Gln 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/acvr1-p-ser290 (accessed [today's date]).

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