Is CDKN1B p.Glu86= (c.258G>A) pathogenic?

CDKN1B p.Glu86= (c.258G>A) is classified Benign in CDKN1B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.23%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Glu86= (c.258G>A)?

CDKN1B p.Glu86= (c.258G>A) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

How common is CDKN1B p.Glu86= (c.258G>A) in the general population?

CDKN1B p.Glu86= (c.258G>A) is low-frequency (popmax 1.23%, eas) (gnomAD).

CDKN1B p.Glu86=

c.258G>A · rs142940486 · VCV239618

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.23%, eas)

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 2.1	GERP 0.59, phastCons 1
Overall
CADD	8.599	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.23% East Asian · 551/44,884 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0345% 557/1,614,230 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.23%	81
Remaining individualsnot grpmax-eligible	0.0096%	10,418

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.Glu86=
Coding: c.258G>A
MANE Select: NM_004064
dbSNP: rs142940486
Type: single nucleotide variant
Location: chr12:12718097 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 86: the 'interaction with cdk2' region; the 'disordered' region; an α-helix

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

Similar variants

CDKN1B p.Glu86Asp Uncertain significance ★★ ⚠ same residue
CDKN1B p.Glu86Ala Uncertain significance ★ ⚠ same residue
CDKN1B p.Glu86Lys Uncertain significance ★ ⚠ same residue
CDKN1B p.Glu86fs 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

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-glu86 (accessed [today's date]).

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