Is AIP p.Ala2= (c.6G>A) pathogenic?

AIP p.Ala2= (c.6G>A) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-17). Very rare (popmax 0.004%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ala2= (c.6G>A)?

AIP p.Ala2= (c.6G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ala2= (c.6G>A) in the general population?

AIP p.Ala2= (c.6G>A) is very rare (popmax 0.004%, afr) (gnomAD).

AIP p.Ala2=

c.6G>A · rs1865725846 · VCV1626086

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 9.7	GERP 2, phastCons 1
Overall
CADD	17.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,950 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,038 alleles · very rare

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.Ala2=
Coding: c.6G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs1865725846
Type: single nucleotide variant
Location: chr11:67483164 (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

Similar variants

AIP p.Ala2Pro Uncertain significance ★★ ⚠ same residue
AIP p.Ala2Gly Uncertain significance ★ ⚠ same residue
AIP p.Ala2Val 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-ala2 (accessed [today's date]).

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