Is CDKN2AIP p.Val5Met (c.13G>A) pathogenic?

CDKN2AIP p.Val5Met (c.13G>A) is classified Uncertain significance in CDKN2AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely pathogenic (0.7942); Very rare (popmax 0.00289%, nfe).

How common is CDKN2AIP p.Val5Met (c.13G>A) in the general population?

CDKN2AIP p.Val5Met (c.13G>A) is very rare (popmax 0.00289%, nfe) (gnomAD).

What do computational predictors say about CDKN2AIP p.Val5Met (c.13G>A)?

AlphaMissense predicts likely pathogenic (score 0.7942) — an in-silico prediction, not a clinical call.

CDKN2AIP p.Val5Met

c.13G>A · VCV4651620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00289%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7942	likely pathogenic
REVEL	0.244	benign-leaning
SaProt	LLR -9.05	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,183 bp · p 0.0012 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00289% European (non-Finnish) · 33/1,141,336 alleles

Filtering AF 0.00206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.0022% 34/1,544,034 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00289%	34,586
Remaining individualsnot grpmax-eligible	0.00168%	59,592

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.Val5Met
Coding: c.13G>A
MANE Select: NM_017632
Type: single nucleotide variant
Location: chr4:183444810 (GRCh38)
Gene constraint: LOEUF 0.49 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.54

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.Ala47Val Uncertain significance ★ ⚠ same type
CDKN2AIP p.Ala53Val 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-val5met (accessed [today's date]).

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