Is AIP p.Asp262= (c.786C>T) pathogenic?

AIP p.Asp262= (c.786C>T) is classified Likely benign in AIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.017%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Asp262= (c.786C>T)?

AIP p.Asp262= (c.786C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Asp262= (c.786C>T) in the general population?

AIP p.Asp262= (c.786C>T) is ultra-rare (popmax 0.017%, mid) (gnomAD).

AIP p.Asp262=

c.786C>T · rs777095131 · VCV485055

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

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 -12	GERP -3.6
Overall
CADD	0.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% Middle Eastern · 1/5,886 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00248% 40/1,609,980 alleles · ultra-rare exomes 33/1,457,656 · genomes 7/152,324 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,886
Admixed American	0.00333%	30,007
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0032%	31,226
European (non-Finnish)	0.00254%	39,333
Finnishnot grpmax-eligible	0.00166%	60,118
African / African-American	0.00133%	75,048

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.Asp262=
Coding: c.786C>T
MANE Select: NM_003977
dbSNP: rs777095131
Type: single nucleotide variant
Location: chr11:67490456 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 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.Asp262Asn Uncertain significance ★★ ⚠ same residue
AIP p.Asp262Glu Uncertain significance ★★ ⚠ same residue
AIP p.Asp262His Uncertain significance ★★ ⚠ same residue
AIP p.Asp262Gly Uncertain significance ★ ⚠ same residue
AIP p.Asp262Val Uncertain significance ★ ⚠ same residue
AIP p.Asp262Tyr Uncertain significance ★ ⚠ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
AIP p.Arg304Ter 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-asp262 (accessed [today's date]).

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