Is AIP p.Tyr203= (c.609C>T) pathogenic?

AIP p.Tyr203= (c.609C>T) is classified Benign/Likely benign in AIP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0439%, sas); Associated with growth hormone secreting pituitary adenoma 1.

What condition is associated with AIP p.Tyr203= (c.609C>T)?

AIP p.Tyr203= (c.609C>T) is associated with growth hormone secreting pituitary adenoma 1, hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Tyr203= (c.609C>T) in the general population?

AIP p.Tyr203= (c.609C>T) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

How is Familial isolated pituitary adenoma inherited?

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

AIP p.Tyr203=

c.609C>T · rs146317385 · VCV485065

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

Conditions

growth hormone secreting pituitary adenoma 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.6
Overall
CADD	2.679	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% South Asian · 40/91,082 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.0114% 184/1,613,136 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
East Asian	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.0288%	3,471
European (non-Finnish)	0.00915%	10,926
African / African-American	0.00534%	18,724

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.Tyr203=
Coding: c.609C>T
MANE Select: NM_003977
dbSNP: rs146317385
Type: single nucleotide variant
Location: chr11:67490178 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 203: an α-helix

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.Tyr203Cys Uncertain significance ★★ ⚠ same residue
AIP p.Tyr203His Uncertain significance ★★ ⚠ same residue
AIP p.Tyr203Ter Pathogenic ★ same residue
AIP p.Tyr203Asn Uncertain significance ★ same residue
AIP p.Tyr203Asp Uncertain significance ★ ⚠ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
AIP p.Arg304Ter Pathogenic ★★ same condition
AIP p.Arg81Ter 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-tyr203 (accessed [today's date]).

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