Is AIP p.Gln239Pro (c.716A>C) pathogenic?

AIP p.Gln239Pro (c.716A>C) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-19). AlphaMissense: likely pathogenic (0.9841); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Gln239Pro (c.716A>C)?

AIP p.Gln239Pro (c.716A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Gln239Pro (c.716A>C) in the general population?

AIP p.Gln239Pro (c.716A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Gln239Pro (c.716A>C)?

AlphaMissense predicts likely pathogenic (score 0.9841) — an in-silico prediction, not a clinical call.

AIP p.Gln239Pro

c.716A>C · VCV4868492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9841	likely pathogenic · top 7% in AIP
REVEL	0.9	moderately pathogenic-leaning
SaProt	LLR -14.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AIP
Protein: p.Gln239Pro
Coding: c.716A>C
MANE Select: NM_003977
Type: single nucleotide variant
Location: chr11:67490386 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 239: 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

Similar variants

AIP p.Gln239Arg Uncertain significance ★★ ⚠ same residue
AIP p.Gln239fs Pathogenic ★★ same residue
AIP p.Gln239= Likely benign ★ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
AIP p.Arg304Ter Pathogenic ★★ same condition
AIP p.Arg81Ter Pathogenic ★★ same condition
AIP p.Cys238Tyr Likely pathogenic ★★ same condition
AIP p.Gln126Ter 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-gln239pro (accessed [today's date]).

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