Is AIP p.Ala276Val (c.827C>T) pathogenic?

AIP p.Ala276Val (c.827C>T) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-28). AlphaMissense: likely benign (0.2263); Ultra-rare (popmax 0.0307%, afr); Associated with growth hormone secreting pituitary adenoma 1.

What condition is associated with AIP p.Ala276Val (c.827C>T)?

AIP p.Ala276Val (c.827C>T) is associated with growth hormone secreting pituitary adenoma 1, acroleukopathy, symmetric, Cushing disease due to pituitary adenoma (ClinVar).

How common is AIP p.Ala276Val (c.827C>T) in the general population?

AIP p.Ala276Val (c.827C>T) is ultra-rare (popmax 0.0307%, 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.Ala276Val (c.827C>T)?

AlphaMissense predicts likely benign (score 0.2263) — an in-silico prediction, not a clinical call.

AIP p.Ala276Val

c.827C>T · rs61741147 · VCV485056

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2263 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

growth hormone secreting pituitary adenoma 1

Computational evidence

Protein change
AlphaMissense	0.2263	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -8.98	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 7.6	GERP 2, phastCons 1
Overall
CADD	21.5	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 0.0307% African / African-American · 23/74,928 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00341% 55/1,612,630 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,258
South Asian	0.00329%	30,359
European (non-Finnish)	0.00229%	43,703
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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.Ala276Val
Coding: c.827C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs61741147
Type: single nucleotide variant
Location: chr11:67490827 (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: acroleukopathy, symmetric Cushing disease due to pituitary adenoma hereditary neoplastic syndrome

For Familial isolated pituitary adenoma (Orphanet):

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

Similar variants

AIP p.Ala276Gly Uncertain significance ★★ ⚠ same residue
AIP p.Ala276Thr Uncertain significance ★★ ⚠ same residue
AIP p.Ala276= Likely benign ★★ 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-ala276val (accessed [today's date]).

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