Is CDKN1C p.Arg65Ser (c.193C>A) pathogenic?

CDKN1C p.Arg65Ser (c.193C>A) is classified Uncertain significance in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.9735); No allele count reported in gnomAD v4.1 (AN 1,574,980).

How common is CDKN1C p.Arg65Ser (c.193C>A) in the general population?

CDKN1C p.Arg65Ser (c.193C>A) is no allele count reported in gnomAD v4.1 (AN 1,574,980) (gnomAD).

What do computational predictors say about CDKN1C p.Arg65Ser (c.193C>A)?

AlphaMissense predicts likely pathogenic (score 0.9735) — an in-silico prediction, not a clinical call.

CDKN1C p.Arg65Ser

c.193C>A · rs750526402 · VCV3252784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9735 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,574,980)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9735	likely pathogenic · top 9% in CDKN1C
REVEL	0.492	indeterminate
SaProt	LLR -9.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.8	GERP 0.96, phastCons 1
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R76S vs ClinVar R65S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,574,980). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKN1C
Protein: p.Arg65Ser
Coding: c.193C>A
MANE Select: NM_001122630
dbSNP: rs750526402
Type: single nucleotide variant
Location: chr11:2885264 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93

Full CDKN1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN1C p.Arg65Cys Uncertain significance ★★ ⚠ same residue
CDKN1C p.Arg65Leu Uncertain significance ★ ⚠ same residue
CDKN1C p.Arg65= Likely benign ★ same residue
CDKN1C p.Arg268Ser Likely pathogenic ★★ ⚠ same type
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same type
CDKN1C p.Cys19Ter Pathogenic/Likely pathogenic ★★ same type
CDKN1C p.Gln219Ter Pathogenic ★★ same type
CDKN1C p.Gln221Ter Pathogenic ★★ 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/cdkn1c-p-arg65ser (accessed [today's date]).

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