Is CDKN1B p.Arg93= (c.279G>A) pathogenic?

CDKN1B p.Arg93= (c.279G>A) is classified Conflicting classifications of pathogenicity in CDKN1B (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-23). Very rare (popmax 0.000847%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Arg93= (c.279G>A)?

CDKN1B p.Arg93= (c.279G>A) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4, hereditary nonpolyposis colon cancer (ClinVar).

How common is CDKN1B p.Arg93= (c.279G>A) in the general population?

CDKN1B p.Arg93= (c.279G>A) is very rare (popmax 0.000847%, nfe) (gnomAD).

CDKN1B p.Arg93=

c.279G>A · rs766901538 · VCV412882

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

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 0.78	GERP 1.6, phastCons 1
Overall
CADD	7.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,180,054 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,614,042 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: CDKN1B
Protein: p.Arg93=
Coding: c.279G>A
MANE Select: NM_004064
dbSNP: rs766901538
Type: single nucleotide variant
Location: chr12:12718118 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 93: the 'disordered' region

Full CDKN1B 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

Also linked: multiple endocrine neoplasia type 4 hereditary nonpolyposis colon cancer

Similar variants

CDKN1B p.Arg93Gln Uncertain significance ★★ ⚠ same residue
CDKN1B p.Arg93Trp Benign/Likely benign ★★ same residue
CDKN1B p.Arg93fs Pathogenic ★ same residue
CDKN1B p.Arg154Ter Pathogenic ★★ same condition
CDKN1B p.Arg5Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1B p.Gln104Ter Pathogenic ★★ same condition
CDKN1B p.Gln107Ter Pathogenic ★★ same condition
CDKN1B p.Gln141Ter 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/cdkn1b-p-arg93 (accessed [today's date]).

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