Is AIP p.Lys316del (c.946_948del) pathogenic?

AIP p.Lys316del (c.946948del) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-17). Very rare (popmax 0.00102%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Lys316del (c.946_948del)?

AIP p.Lys316del (c.946_948del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Lys316del (c.946_948del) in the general population?

AIP p.Lys316del (c.946_948del) is very rare (popmax 0.00102%, nfe) (gnomAD).

AIP p.Lys316del

c.946_948del · rs766251663 · VCV823266

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 0.84, phastCons 1
Overall
CADD	15.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,716 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00161% 26/1,612,024 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0223%	4,474
European (non-Finnish)grpmax	0.00102%	98,310

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys316del
Coding: c.946_948del
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs766251663
Type: Deletion
Location: chr11:67490944 (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.Lys316= Likely benign ★ 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
AIP c.100-4del Likely benign ★★ same condition
AIP p.Arg119fs 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-lys316del (accessed [today's date]).

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