Is AIP p.Val101Met (c.301G>A) pathogenic?

AIP p.Val101Met (c.301G>A) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-12-23). AlphaMissense: likely pathogenic (0.7169); Rare (popmax 0.237%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Val101Met (c.301G>A)?

AIP p.Val101Met (c.301G>A) is associated with hereditary neoplastic syndrome, growth hormone secreting pituitary adenoma 1 (ClinVar).

How common is AIP p.Val101Met (c.301G>A) in the general population?

AIP p.Val101Met (c.301G>A) is rare (popmax 0.237%, afr) (gnomAD).

What do computational predictors say about AIP p.Val101Met (c.301G>A)?

AlphaMissense predicts likely pathogenic (score 0.7169) — an in-silico prediction, not a clinical call.

AIP p.Val101Met

c.301G>A · rs147931650 · VCV305726

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.7169 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.237%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7169	likely pathogenic
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -11.30	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 9.9	GERP -3.9, phastCons 1
Overall
CADD	29.8	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 0.237% African / African-American · 178/74,972 alleles

Filtering AF 0.209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.198%

Overall 0.0117% 188/1,611,466 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.237%	421
Admixed American	0.00834%	11,994
Remaining individualsnot grpmax-eligible	0.00641%	15,592
European (non-Finnish)	8.48e-05%	1,179,743

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.Val101Met
Coding: c.301G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs147931650
Type: single nucleotide variant
Location: chr11:67489288 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

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.Val101= Likely benign ★ same residue
AIP p.Val101_Leu141del Likely pathogenic ★ 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-val101met (accessed [today's date]).

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