Is ACVR1 p.Leu495fs (c.1483_1484del) pathogenic?

ACVR1 p.Leu495fs (c.14831484del) is classified Uncertain significance in ACVR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). Absent from gnomAD.

How common is ACVR1 p.Leu495fs (c.1483_1484del) in the general population?

ACVR1 p.Leu495fs (c.1483_1484del) is absent from gnomAD (gnomAD).

ACVR1 p.Leu495fs

c.1483_1484del · rs1299357880 · VCV2702296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: ACVR1
Protein: p.Leu495fs
Coding: c.1483_1484del
MANE Select: NM_001111067
dbSNP: rs1299357880
Type: Deletion
Location: chr2:157737577 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.70 · 85 PDB
Residue 495: the protein kinase domain; an α-helix

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

Similar variants

ACVR1 c.332-12_361del Uncertain significance ★ same type
ACVR1 p.His286fs Uncertain significance ★ same type
ACVR1 p.Ile262_Leu263insTer Uncertain significance ★ same type
ACVR1 p.Met34fs Uncertain significance ★ same type
ACVR1 p.Pro482fs Uncertain significance ★ same type
ACVR1 c.1395+20del Likely benign ★ same type
ACVR1 c.644-19del Likely benign ★ same type
ACVR1 c.67+10_67+11del Likely benign ★ 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-leu495fs (accessed [today's date]).

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