Is AIP p.Val96= (c.288C>A) pathogenic?

AIP p.Val96= (c.288C>A) is classified Likely benign in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-15). Very rare (popmax 0.00835%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Val96= (c.288C>A)?

AIP p.Val96= (c.288C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Val96= (c.288C>A) in the general population?

AIP p.Val96= (c.288C>A) is very rare (popmax 0.00835%, amr) (gnomAD).

AIP p.Val96=

c.288C>A · rs761597029 · VCV2902941

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00835%, 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 0.69	GERP -3.9, phastCons 1
Overall
CADD	5.735	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00835% Admixed American · 5/59,896 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000373% 6/1,610,556 alleles · very rare exomes 6/1,458,250 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,979
South Asian	0.0011%	90,884

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.Val96=
Coding: c.288C>A
MANE Select: NM_003977
dbSNP: rs761597029
Type: single nucleotide variant
Location: chr11:67489275 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 96: the ppiase fkbp-type domain

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.Val96Ile 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
AIP p.Gln14Ter Pathogenic ★★ same condition
AIP p.Gln217Ter 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-val96 (accessed [today's date]).

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