Is AIP p.Arg128Cys (c.382C>T) pathogenic?

AIP p.Arg128Cys (c.382C>T) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1586); Rare (popmax 0.18%, afr); Associated with growth hormone secreting pituitary adenoma 1.

What condition is associated with AIP p.Arg128Cys (c.382C>T)?

AIP p.Arg128Cys (c.382C>T) is associated with growth hormone secreting pituitary adenoma 1, hereditary neoplastic syndrome, familial isolated pituitary adenoma (ClinVar).

How common is AIP p.Arg128Cys (c.382C>T) in the general population?

AIP p.Arg128Cys (c.382C>T) is rare (popmax 0.18%, afr) (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.Arg128Cys (c.382C>T)?

AlphaMissense predicts likely benign (score 0.1586) — an in-silico prediction, not a clinical call.

AIP p.Arg128Cys

c.382C>T · rs140530307 · VCV485053

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1586 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.18%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

growth hormone secreting pituitary adenoma 1

Computational evidence

Protein change
AlphaMissense	0.1586	likely benign
REVEL	0.324	indeterminate
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -0.22, phastCons 1
Overall
CADD	25.9	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 0.18% African / African-American · 135/75,048 alleles

Filtering AF 0.155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.146%

Overall 0.00961% 155/1,612,930 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.18%	556
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Admixed American	0.00333%	30,014
Finnishnot grpmax-eligible	0.00159%	62,904
European (non-Finnish)	0.00119%	84,281

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.Arg128Cys
Coding: c.382C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs140530307
Type: single nucleotide variant
Location: chr11:67489369 (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 familial isolated pituitary adenoma

For Familial isolated pituitary adenoma (Orphanet):

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

Similar variants

AIP p.Arg128Gly Uncertain significance ★ ⚠ same residue
AIP p.Arg128His Conflicting classifications of pathogenicity ★ ⚠ same residue
AIP p.Arg128Pro Uncertain significance ★ ⚠ 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

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-arg128cys (accessed [today's date]).

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