Is AIP p.Arg119fs (c.356_371del) pathogenic?

AIP p.Arg119fs (c.356371del) is classified Pathogenic in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Arg119fs (c.356_371del)?

AIP p.Arg119fs (c.356_371del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Arg119fs (c.356_371del) in the general population?

AIP p.Arg119fs (c.356_371del) is very rare (popmax 0.00133%, afr) (gnomAD).

AIP p.Arg119fs

c.356_371del · rs1159928352 · VCV3223610

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -2.1, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,928 alleles

Overall 0.000657% 1/152,228 alleles · very rare

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: AIP
Protein: p.Arg119fs
Coding: c.356_371del
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs1159928352
Type: Deletion
Location: chr11:67489343 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

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

Similar variants

AIP p.Arg119Trp Uncertain significance ★★ ⚠ same residue
AIP p.Arg119= Likely benign ★★ same residue
AIP p.Arg119Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
AIP p.Gln239fs Pathogenic ★★ same condition
AIP p.Lys273fs Pathogenic ★★ same condition
AIP p.Arg325fs Uncertain significance ★★ same condition
AIP p.Asn264del Uncertain significance ★★ same condition
AIP p.Gly47_Arg54del 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/aip-p-arg119fs (accessed [today's date]).

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