Is ACVR1 p.Ala90= (c.270C>T) pathogenic?

ACVR1 p.Ala90= (c.270C>T) is classified Benign in ACVR1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 91.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with fibrodysplasia ossificans progressiva.

What condition is associated with ACVR1 p.Ala90= (c.270C>T)?

ACVR1 p.Ala90= (c.270C>T) is associated with fibrodysplasia ossificans progressiva (ClinVar).

How is Fibrodysplasia ossificans progressiva inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

ACVR1 p.Ala90=

Q: How common is ACVR1 p.Ala90= (c.270C>T) in the general population?

ACVR1 p.Ala90= (c.270C>T) is common (popmax 91.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.270C>T · rs2227861 · VCV257464

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 91.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

fibrodysplasia ossificans progressiva

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 -1.8	GERP -4.1
Overall
CADD	1.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 91.8% East Asian · 41,206/44,876 alleles

Filtering AF 91.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 90.8%

Overall 75% 1,210,844/1,613,950 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	91.8%	1
South Asian	82.7%	1
Ashkenazi Jewishnot grpmax-eligible	80.5%	1
Admixed American	80.3%	1
Finnishnot grpmax-eligible	78.2%	1
European (non-Finnish)	76.3%	1
Middle Eastern	75.6%	1
Remaining individualsnot grpmax-eligible	74.9%	1
Amishnot grpmax-eligible	68.3%	1
African / African-American	25.8%	4

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.Ala90=
Coding: c.270C>T
MANE Select: NM_001111067
dbSNP: rs2227861
Type: single nucleotide variant
Location: chr2:157780398 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.70 · 85 PDB
Residue 90: a β-strand

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

Disease context

fibrodysplasia ossificans progressiva — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fibrodysplasia ossificans progressiva (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

ACVR1 p.Arg206His Pathogenic ★★ same condition
ACVR1 p.Gly328Glu Pathogenic/Likely pathogenic ★★ same condition
ACVR1 p.Gly356Asp Pathogenic/Likely pathogenic ★★ same condition
ACVR1 p.Ser41Phe Uncertain significance ★★ ⚠ same condition
ACVR1 c.1395+5G>A Likely benign ★★ same condition
ACVR1 c.643+7C>T Benign ★★ same condition
ACVR1 c.644-3T>C Benign/Likely benign ★★ same condition
ACVR1 c.68-25T>C Benign ★★ 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/acvr1-p-ala90 (accessed [today's date]).

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