Is AIP p.Arg307fs (c.919dup) pathogenic?

AIP p.Arg307fs (c.919dup) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-01-15). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Arg307fs (c.919dup)?

AIP p.Arg307fs (c.919dup) is associated with hereditary neoplastic syndrome, growth hormone secreting pituitary adenoma 1 (ClinVar).

How common is AIP p.Arg307fs (c.919dup) in the general population?

AIP p.Arg307fs (c.919dup) is no gnomAD frequency available for this variant (gnomAD).

AIP p.Arg307fs

c.919dup · rs267606589 · VCV41215

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

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 (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.2	GERP -0.58, phastCons 0.92

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: AIP
Protein: p.Arg307fs
Coding: c.919dup
MANE Select: NM_003977
dbSNP: rs267606589
Type: Duplication
Location: chr11:67490918 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 307: a UniProt-annotated variant site (in); an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: growth hormone secreting pituitary adenoma 1

Similar variants

AIP p.Arg307Trp Uncertain significance ★★ ⚠ same residue
AIP p.Arg307= Uncertain significance ★ same residue
AIP p.Arg307Gly Uncertain significance ★ ⚠ same residue
AIP p.Phe269_His275dup Pathogenic ★★ same condition
AIP p.Gln282fs Likely pathogenic ★ same condition
AIP p.Ile76fs Pathogenic ★ same condition
AIP p.Phe68fs Pathogenic ★ same condition
AIP p.Pro147fs Pathogenic ★ 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/aip-p-arg307fs (accessed [today's date]).

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