Is CDKN1B p.Glu78= (c.234G>A) pathogenic?

CDKN1B p.Glu78= (c.234G>A) is classified Benign/Likely benign in CDKN1B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-22). Ultra-rare (popmax 0.0111%, nfe); Associated with multiple endocrine neoplasia type 4.

What condition is associated with CDKN1B p.Glu78= (c.234G>A)?

CDKN1B p.Glu78= (c.234G>A) is associated with multiple endocrine neoplasia type 4, hereditary neoplastic syndrome (ClinVar).

How common is CDKN1B p.Glu78= (c.234G>A) in the general population?

CDKN1B p.Glu78= (c.234G>A) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

How is Multiple endocrine neoplasia type 4 inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CDKN1B p.Glu78=

c.234G>A · rs751794433 · VCV307661

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Conditions

multiple endocrine neoplasia type 4

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 4.8	GERP 1.6, phastCons 1
Overall
CADD	11.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% European (non-Finnish) · 131/1,180,048 alleles

Filtering AF 0.00952% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00896%

Overall 0.00997% 161/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,230
Finnishnot grpmax-eligible	0.0219%	4,575
Remaining individualsnot grpmax-eligible	0.0112%	8,927
European (non-Finnish)grpmax	0.0111%	9,008
African / African-American	0.00133%	74,944
South Asian	0.0011%	91,092

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu78=
Coding: c.234G>A
MANE Select: NM_004064
dbSNP: rs751794433
Type: single nucleotide variant
Location: chr12:12718073 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 78: the 'interaction with cdk2' region; a β-strand

Full CDKN1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple endocrine neoplasia type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Multiple endocrine neoplasia type 4 (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

Similar variants

CDKN1B p.Glu78Asp Uncertain significance ★★ ⚠ same residue
CDKN1B p.Glu78Gln Uncertain significance ★★ ⚠ same residue
CDKN1B p.Glu78Lys Uncertain significance ★★ ⚠ same residue
CDKN1B p.Glu78Ala Uncertain significance ★ ⚠ same residue
CDKN1B p.Glu78fs Pathogenic ★ same residue
CDKN1B p.Arg154Ter Pathogenic ★★ same condition
CDKN1B p.Arg5Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1B p.Gln104Ter 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-glu78 (accessed [today's date]).

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