Is AIP p.Asp262Asn (c.784G>A) pathogenic?

AIP p.Asp262Asn (c.784G>A) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-31). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.00446%, eas); Associated with growth hormone secreting pituitary adenoma 1.

What condition is associated with AIP p.Asp262Asn (c.784G>A)?

AIP p.Asp262Asn (c.784G>A) is associated with growth hormone secreting pituitary adenoma 1, hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Asp262Asn (c.784G>A) in the general population?

AIP p.Asp262Asn (c.784G>A) is very rare (popmax 0.00446%, eas) (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.Asp262Asn (c.784G>A)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

AIP p.Asp262Asn

c.784G>A · rs758918509 · VCV938119

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

growth hormone secreting pituitary adenoma 1

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.698	pathogenic-leaning
SaProt	LLR -6.27	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.68	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	22.7	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 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00171% 25/1,458,240 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,441
European (non-Finnish)	0.00186%	53,636
South Asian	0.0011%	91,078

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.Asp262Asn
Coding: c.784G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs758918509
Type: single nucleotide variant
Location: chr11:67490454 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

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

Disease context

growth hormone secreting pituitary adenoma 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Familial isolated pituitary adenoma (Orphanet):

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

Similar variants

AIP p.Asp262Glu Uncertain significance ★★ ⚠ same residue
AIP p.Asp262His Uncertain significance ★★ ⚠ same residue
AIP p.Asp262= Likely benign ★★ same residue
AIP p.Asp262Gly Uncertain significance ★ ⚠ same residue
AIP p.Asp262Val Uncertain significance ★ ⚠ same residue
AIP p.Asp262Tyr 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-asp262asn (accessed [today's date]).

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