Is AIP p.Gln217Arg (c.650A>G) pathogenic?

AIP p.Gln217Arg (c.650A>G) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-28). AlphaMissense: likely benign (0.1261); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Gln217Arg (c.650A>G)?

AIP p.Gln217Arg (c.650A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Gln217Arg (c.650A>G) in the general population?

AIP p.Gln217Arg (c.650A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Gln217Arg (c.650A>G)?

AlphaMissense predicts likely benign (score 0.1261) — an in-silico prediction, not a clinical call.

AIP p.Gln217Arg

c.650A>G · rs1865878548 · VCV1448289

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1261 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,456)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1261	likely benign
REVEL	0.359	indeterminate
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.72	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,456). 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.Gln217Arg
Coding: c.650A>G
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs1865878548
Type: single nucleotide variant
Location: chr11:67490320 (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.Gln217Ter Pathogenic ★★ same residue
AIP p.Gln217Lys Uncertain significance ★★ ⚠ same residue
AIP p.Gln217Leu Uncertain significance ★ same residue
AIP p.Gln217= Likely benign ★ same residue
AIP p.Gln217Glu Uncertain significance ★ ⚠ same residue
AIP p.Gln217His Uncertain significance ★ ⚠ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
AIP p.Arg304Ter 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-gln217arg (accessed [today's date]).

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