Is AIP p.Gln143Arg (c.428A>G) pathogenic?

AIP p.Gln143Arg (c.428A>G) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-11). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.00167%, amr); Associated with AIP-related disorder.

What condition is associated with AIP p.Gln143Arg (c.428A>G)?

AIP p.Gln143Arg (c.428A>G) is associated with AIP-related disorder, hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Gln143Arg (c.428A>G) in the general population?

AIP p.Gln143Arg (c.428A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AIP p.Gln143Arg (c.428A>G)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

AIP p.Gln143Arg

c.428A>G · rs954223621 · VCV841955

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AIP-related disorder

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 2, phastCons 1
Overall
CADD	18.47	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

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Overall 0.000657% 1/152,226 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.Gln143Arg
Coding: c.428A>G
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs954223621
Type: single nucleotide variant
Location: chr11:67489415 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB
Residue 143: an α-helix

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

Disease context

AIP-related disorder

Also linked: hereditary neoplastic syndrome

Similar variants

AIP p.Gln143Glu Uncertain significance ★★ ⚠ same residue
AIP p.Gln143Ter Pathogenic ★ 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
AIP p.Gln14Ter 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-gln143arg (accessed [today's date]).

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