Is ACVR1 p.Ile352Val (c.1054A>G) pathogenic?

ACVR1 p.Ile352Val (c.1054A>G) is classified Uncertain significance in ACVR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-11). AlphaMissense: likely benign (0.1599); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACVR1 p.Ile352Val (c.1054A>G)?

ACVR1 p.Ile352Val (c.1054A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACVR1 p.Ile352Val (c.1054A>G) in the general population?

ACVR1 p.Ile352Val (c.1054A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ACVR1 p.Ile352Val (c.1054A>G)?

AlphaMissense predicts likely benign (score 0.1599) — an in-silico prediction, not a clinical call.

ACVR1 p.Ile352Val

c.1054A>G · rs1325945796 · VCV2619024

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1599 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1599	likely benign
REVEL	0.768	pathogenic-leaning
SaProt	LLR -9.45	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.8, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 13 kb · p 3.6e-12 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000743% 12/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
European (non-Finnish)	0.000932%	107,275

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.Ile352Val
Coding: c.1054A>G
MANE Select: NM_001111067
dbSNP: rs1325945796
Type: single nucleotide variant
Location: chr2:157765933 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.70 · 85 PDB
Residue 352: a β-strand; the protein kinase domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACVR1 p.Gly328Glu Pathogenic/Likely pathogenic ★★ same condition
ACVR1 p.Arg147Gln Uncertain significance ★★ ⚠ same condition
ACVR1 p.Arg307Gln Uncertain significance ★★ ⚠ same condition
ACVR1 p.Arg417Gln Uncertain significance ★★ ⚠ same condition
ACVR1 p.Gly39Val Uncertain significance ★★ ⚠ same condition
ACVR1 p.His121Tyr Uncertain significance ★★ ⚠ same condition
ACVR1 p.Ile236Leu Uncertain significance ★★ ⚠ same condition
ACVR1 p.Lys446Asn 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/acvr1-p-ile352val (accessed [today's date]).

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