Is AIP p.Arg9Gln (c.26G>A) pathogenic?

AIP p.Arg9Gln (c.26G>A) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0758); Rare (popmax 0.165%, mid); Associated with acroleukopathy, symmetric.

What condition is associated with AIP p.Arg9Gln (c.26G>A)?

AIP p.Arg9Gln (c.26G>A) is associated with acroleukopathy, symmetric, growth hormone secreting pituitary adenoma 1, Cushing disease due to pituitary adenoma (ClinVar).

How common is AIP p.Arg9Gln (c.26G>A) in the general population?

AIP p.Arg9Gln (c.26G>A) is rare (popmax 0.165%, mid) (gnomAD).

What do computational predictors say about AIP p.Arg9Gln (c.26G>A)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

AIP p.Arg9Gln

c.26G>A · rs139459091 · VCV485052

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acroleukopathy, symmetric

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -6.44	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 8.5	GERP 0.81, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% Middle Eastern · 10/6,062 alleles

Filtering AF 0.0902% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0823%

Overall 0.0215% 347/1,614,204 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	606
Admixed American	0.112%	896
Remaining individualsnot grpmax-eligible	0.056%	1,786
European (non-Finnish)	0.0192%	5,198
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,868
African / African-American	0.00266%	37,537
South Asian	0.0022%	45,543
Finnishnot grpmax-eligible	0.00156%	64,024

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.Arg9Gln
Coding: c.26G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs139459091
Type: single nucleotide variant
Location: chr11:67483184 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

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

Disease context

acroleukopathy, symmetric — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: growth hormone secreting pituitary adenoma 1 Cushing disease due to pituitary adenoma hereditary neoplastic syndrome

Similar variants

AIP p.Arg9Trp Uncertain significance ★★ ⚠ same residue
AIP p.Arg9Leu Uncertain significance ★ ⚠ same residue
AIP p.Arg9Gly Uncertain significance ★ ⚠ same residue
AIP p.Arg9= 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

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-arg9gln (accessed [today's date]).

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