Is AIP p.Phe269= (c.807C>T) pathogenic?

AIP p.Phe269= (c.807C>T) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-02-03). Rare (popmax 0.125%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Phe269= (c.807C>T)?

AIP p.Phe269= (c.807C>T) is associated with hereditary neoplastic syndrome, growth hormone secreting pituitary adenoma 1 (ClinVar).

How common is AIP p.Phe269= (c.807C>T) in the general population?

AIP p.Phe269= (c.807C>T) is rare (popmax 0.125%, nfe) (gnomAD).

AIP p.Phe269=

c.807C>T · rs139407567 · VCV41209

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.125%, nfe)

Conditions

hereditary neoplastic syndrome

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 4	GERP 2, phastCons 1
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.125% European (non-Finnish) · 1,477/1,179,956 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.103% 1,659/1,612,406 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.125%	799
Remaining individualsnot grpmax-eligible	0.0881%	1,135
South Asian	0.0879%	1,138
Admixed American	0.0367%	2,728
Middle Eastern	0.0352%	2,837
African / African-American	0.0267%	3,752
Finnishnot grpmax-eligible	0.00477%	20,951

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.Phe269=
Coding: c.807C>T
MANE Select: NM_003977
dbSNP: rs139407567
Type: single nucleotide variant
Location: chr11:67490807 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 269: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: growth hormone secreting pituitary adenoma 1

Similar variants

AIP p.Phe269_His275dup Pathogenic ★★ same residue
AIP p.Phe269Leu 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
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-phe269 (accessed [today's date]).

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