Is AIP p.Cys240Arg (c.718T>C) pathogenic?

AIP p.Cys240Arg (c.718T>C) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely pathogenic (0.9969); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Cys240Arg (c.718T>C)?

AIP p.Cys240Arg (c.718T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Cys240Arg (c.718T>C) in the general population?

AIP p.Cys240Arg (c.718T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AIP p.Cys240Arg (c.718T>C)?

AlphaMissense predicts likely pathogenic (score 0.9969) — an in-silico prediction, not a clinical call.

AIP p.Cys240Arg

c.718T>C · rs2495407193 · VCV2586852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9969 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9969	likely pathogenic · top 1% in AIP
REVEL	0.911	moderately pathogenic-leaning
SaProt	LLR -14.95	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 6.1	GERP 0.84, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.85e-05% 1/1,460,402 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.Cys240Arg
Coding: c.718T>C
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs2495407193
Type: single nucleotide variant
Location: chr11:67490388 (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.Cys240Ser Uncertain significance ★★ ⚠ same residue
AIP p.Cys240Tyr Uncertain significance ★★ ⚠ same residue
AIP p.Cys240= Likely benign ★★ same residue
AIP p.Cys240Trp 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

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-cys240arg (accessed [today's date]).

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