Is AIP p.Arg16His (c.47G>A) pathogenic?

AIP p.Arg16His (c.47G>A) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0748); Rare (popmax 0.306%, nfe); Associated with familial isolated pituitary adenoma.

What condition is associated with AIP p.Arg16His (c.47G>A)?

AIP p.Arg16His (c.47G>A) is associated with familial isolated pituitary adenoma, growth hormone secreting pituitary adenoma 1, hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Arg16His (c.47G>A) in the general population?

AIP p.Arg16His (c.47G>A) is rare (popmax 0.306%, nfe) (gnomAD).

How is Familial isolated pituitary adenoma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AIP p.Arg16His (c.47G>A)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

AIP p.Arg16His

c.47G>A · rs145047094 · VCV41184

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.306%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial isolated pituitary adenoma

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -9.01	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.81, phastCons 1
Overall
CADD	27.8	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 0.306% European (non-Finnish) · 3,606/1,180,018 alleles

Filtering AF 0.297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.294%

Overall 0.245% 3,948/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.306%	327
Finnishnot grpmax-eligible	0.217%	461
Remaining individualsnot grpmax-eligible	0.174%	573
Admixed American	0.0966%	1,035
African / African-American	0.0346%	2,887
Middle Eastern	0.0165%	6,062
South Asian	0.00878%	11,386
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Arg16His
Coding: c.47G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs145047094
Type: single nucleotide variant
Location: chr11:67483205 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

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

Disease context

familial isolated pituitary adenoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: growth hormone secreting pituitary adenoma 1 hereditary neoplastic syndrome

For Familial isolated pituitary adenoma (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly, Infancy

Similar variants

AIP p.Arg16Cys Uncertain significance ★★ ⚠ same residue
AIP p.Arg16= 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
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-arg16his (accessed [today's date]).

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