Is CDKN1C p.Arg268Ser (c.802C>A) pathogenic?

CDKN1C p.Arg268Ser (c.802C>A) is classified Likely pathogenic in CDKN1C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.9957); Absent from gnomAD v4.1; Associated with Monogenic short statue.

What condition is associated with CDKN1C p.Arg268Ser (c.802C>A)?

CDKN1C p.Arg268Ser (c.802C>A) is associated with Monogenic short statue, IMAGe syndrome (ClinVar).

How common is CDKN1C p.Arg268Ser (c.802C>A) in the general population?

CDKN1C p.Arg268Ser (c.802C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN1C p.Arg268Ser (c.802C>A)?

AlphaMissense predicts likely pathogenic (score 0.9957) — an in-silico prediction, not a clinical call.

CDKN1C p.Arg268Ser

c.802C>A · rs1848883206 · VCV986832

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9957 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,499,106)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Monogenic short statue

Computational evidence

Protein change
AlphaMissense	0.9957	likely pathogenic ✓ concordant with ClinVar · top 3% in CDKN1C
REVEL	0.572	indeterminate
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP -0.39, phastCons 1
Overall
CADD	26.7	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 R279S vs ClinVar R268S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,499,106). 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.Arg268Ser
Coding: c.802C>A
MANE Select: NM_001122630
dbSNP: rs1848883206
Type: single nucleotide variant
Location: chr11:2884120 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 268: a modified residue (phosphoserine)

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

Disease context

Monogenic short statue

Also linked: IMAGe syndrome

Similar variants

CDKN1C p.Arg268Cys Uncertain significance ★★ ⚠ same residue
CDKN1C p.Arg268Leu Pathogenic ★ same residue
CDKN1C p.Arg268Pro Pathogenic ⚠ same residue
CDKN1C p.Arg268His Likely pathogenic ★ ⚠ same residue
CDKN1C p.Arg268= Likely benign ★ same residue
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same condition
CDKN1C c.788-3C>T Uncertain significance ★★ same condition
CDKN1C c.-10-13C>T Uncertain significance ★★ ⚠ 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/cdkn1c-p-arg268ser (accessed [today's date]).

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