Is CDKN2B p.Asp118Ala (c.353A>C) pathogenic?

CDKN2B p.Asp118Ala (c.353A>C) is classified Uncertain significance in CDKN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.3379); Very rare (popmax 0.000509%, nfe).

How common is CDKN2B p.Asp118Ala (c.353A>C) in the general population?

CDKN2B p.Asp118Ala (c.353A>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about CDKN2B p.Asp118Ala (c.353A>C)?

AlphaMissense predicts likely benign (score 0.3379) — an in-silico prediction, not a clinical call.

CDKN2B p.Asp118Ala

c.353A>C · rs1821163555 · VCV3141667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3379 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3379	likely benign
REVEL	0.415	indeterminate
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 2,963 bp · p 0.034 · regional, not allelic
Overall
CADD	24.5	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 0.000509% European (non-Finnish) · 6/1,179,608 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000374% 6/1,605,468 alleles · very rare exomes 6/1,453,134 · genomes 0/152,334 · joint denominator

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: CDKN2B
Protein: p.Asp118Ala
Coding: c.353A>C
MANE Select: NM_004936
dbSNP: rs1821163555
Type: single nucleotide variant
Location: chr9:22006051 (GRCh38)
Gene constraint: LOEUF 1.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.12

Full CDKN2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN2B p.Asp118Asn Uncertain significance ★ ⚠ same residue
CDKN2B c.157-102G>A Benign ★★ same type
CDKN2B c.157-27C>A Benign ★★ same type
CDKN2B p.Ala120= Benign ★★ same type
CDKN2B p.Leu115= Likely benign ★★ same type
CDKN2B p.Ala129Gly Uncertain significance ★ ⚠ same type
CDKN2B p.Ala129Val Uncertain significance ★ ⚠ same type
CDKN2B p.Ala23Val 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/cdkn2b-p-asp118ala (accessed [today's date]).

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