Is AIP p.Asp139= (c.417C>T) pathogenic?

AIP p.Asp139= (c.417C>T) is classified Likely benign in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-12). Very rare (popmax 0.00833%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Asp139= (c.417C>T)?

AIP p.Asp139= (c.417C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Asp139= (c.417C>T) in the general population?

AIP p.Asp139= (c.417C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

AIP p.Asp139=

c.417C>T · rs149570102 · VCV1114584

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

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 -11	GERP -3.9
Overall
CADD	10.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,008 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000682% 11/1,612,776 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000424%	235,991

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.Asp139=
Coding: c.417C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs149570102
Type: single nucleotide variant
Location: chr11:67489404 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB
Residue 139: 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

Similar variants

AIP p.Asp139Glu Uncertain significance ★★ ⚠ same residue
AIP p.Asp139Tyr Uncertain significance ★★ ⚠ same residue
AIP p.Asp139His 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-asp139 (accessed [today's date]).

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