Is CDKN2AIP p.Ala47Val (c.140C>T) pathogenic?

CDKN2AIP p.Ala47Val (c.140C>T) is classified Uncertain significance in CDKN2AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.0781); Ultra-rare (popmax 0.0267%, afr).

How common is CDKN2AIP p.Ala47Val (c.140C>T) in the general population?

CDKN2AIP p.Ala47Val (c.140C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about CDKN2AIP p.Ala47Val (c.140C>T)?

AlphaMissense predicts likely benign (score 0.0781) — an in-silico prediction, not a clinical call.

CDKN2AIP p.Ala47Val

c.140C>T · rs777022788 · VCV3141652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0781 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0781	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -1.1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,183 bp · p 0.0012 · regional, not allelic
Overall
CADD	18.54	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0267% African / African-American · 20/74,900 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0013% 21/1,611,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,745
Admixed American	0.00167%	59,900

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: CDKN2AIP
Protein: p.Ala47Val
Coding: c.140C>T
MANE Select: NM_017632
dbSNP: rs777022788
Type: single nucleotide variant
Location: chr4:183444937 (GRCh38)
Gene constraint: LOEUF 0.49 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.54
Residue 47: the xrn2-binding (xtbd) domain

Full CDKN2AIP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN2AIP p.Ala104Ser Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala163Thr Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala281Pro Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala315Ser Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala327Gly Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala367Val Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala53Val Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala55Pro Uncertain significance ★ ⚠ same type

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/cdkn2aip-p-ala47val (accessed [today's date]).

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