Is CDKN1B p.Ser10Arg (c.30C>G) pathogenic?

CDKN1B p.Ser10Arg (c.30C>G) is classified Uncertain significance in CDKN1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-04). AlphaMissense: likely pathogenic (0.9916); Absent from gnomAD v4.1; Associated with multiple endocrine neoplasia type 4.

What condition is associated with CDKN1B p.Ser10Arg (c.30C>G)?

CDKN1B p.Ser10Arg (c.30C>G) is associated with multiple endocrine neoplasia type 4, hereditary neoplastic syndrome (ClinVar).

How common is CDKN1B p.Ser10Arg (c.30C>G) in the general population?

CDKN1B p.Ser10Arg (c.30C>G) is absent from gnomAD v4.1 (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.

What do computational predictors say about CDKN1B p.Ser10Arg (c.30C>G)?

AlphaMissense predicts likely pathogenic (score 0.9916) — an in-silico prediction, not a clinical call.

CDKN1B p.Ser10Arg

c.30C>G · rs990433180 · VCV1439592

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9916 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

multiple endocrine neoplasia type 4

Computational evidence

Protein change
AlphaMissense	0.9916	likely pathogenic · top 3% in CDKN1B
REVEL	0.572	indeterminate
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -0.51, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 1,103 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN1B
Protein: p.Ser10Arg
Coding: c.30C>G
MANE Select: NM_004064
dbSNP: rs990433180
Type: single nucleotide variant
Location: chr12:12717869 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 10: the 'disordered' region; a modified residue (phosphoserine; by uhmk1)

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.Ser10Asn Uncertain significance ★★ ⚠ same residue
CDKN1B p.Ser10Thr Uncertain significance ★★ same residue
CDKN1B p.Ser10= Likely benign ★★ same residue
CDKN1B p.Ser10del Uncertain significance ★★ same residue
CDKN1B p.Ser10fs Likely 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-ser10arg (accessed [today's date]).

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