Is AIP p.Arg271Trp (c.811C>T) pathogenic?

AIP p.Arg271Trp (c.811C>T) is classified Pathogenic/Likely pathogenic in AIP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-06). AlphaMissense: likely pathogenic (0.9513); Very rare (popmax 0.0011%, sas); Associated with familial isolated pituitary adenoma.

What condition is associated with AIP p.Arg271Trp (c.811C>T)?

AIP p.Arg271Trp (c.811C>T) is associated with familial isolated pituitary adenoma, growth hormone secreting pituitary adenoma 1, hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Arg271Trp (c.811C>T) in the general population?

AIP p.Arg271Trp (c.811C>T) is very rare (popmax 0.0011%, sas) (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.Arg271Trp (c.811C>T)?

AlphaMissense predicts likely pathogenic (score 0.9513) — an in-silico prediction, not a clinical call.

AIP p.Arg271Trp

c.811C>T · rs267606579 · VCV41210

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial isolated pituitary adenoma

Computational evidence

Protein change
AlphaMissense	0.9513	likely pathogenic ✓ concordant with ClinVar
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -13.08	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 2.2	GERP -1.6, phastCons 1
Overall
CADD	25.0	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 0.0011% South Asian · 1/91,052 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,460,118 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,052
European (non-Finnish)	0.000339%	294,988

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.Arg271Trp
Coding: c.811C>T
MANE Select: NM_003977
dbSNP: rs267606579
Type: single nucleotide variant
Location: chr11:67490811 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 271: a UniProt-annotated variant site (in pita1; uncertain significance); an α-helix

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.Arg271Gln Uncertain significance ★★ ⚠ same residue
AIP p.Arg271= Likely benign ★ same residue
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
AIP p.Gln217Ter 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-arg271trp (accessed [today's date]).

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