Is CDKN1C p.Phe265Val (c.793T>G) pathogenic?

CDKN1C p.Phe265Val (c.793T>G) is classified Pathogenic in CDKN1C (ClinVar, No assertion criteria, 2 submitters; last evaluated 2012-05-27). AlphaMissense: likely pathogenic (0.9868); Absent from gnomAD v4.1; Associated with IMAGe syndrome.

What condition is associated with CDKN1C p.Phe265Val (c.793T>G)?

CDKN1C p.Phe265Val (c.793T>G) is associated with IMAGe syndrome (ClinVar).

How common is CDKN1C p.Phe265Val (c.793T>G) in the general population?

CDKN1C p.Phe265Val (c.793T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN1C p.Phe265Val (c.793T>G)?

AlphaMissense predicts likely pathogenic (score 0.9868) — an in-silico prediction, not a clinical call.

CDKN1C p.Phe265Val

c.793T>G · rs387907223 · VCV35528

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9868 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

IMAGe syndrome

Computational evidence

Protein change
AlphaMissense	0.9868	likely pathogenic ✓ concordant with ClinVar · top 6% in CDKN1C
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -10.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.77, phastCons 1
Overall
CADD	28.5	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 F276V vs ClinVar F265V) — verify the residue.

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: CDKN1C
Protein: p.Phe265Val
Coding: c.793T>G
MANE Select: NM_001122630
dbSNP: rs387907223
Type: single nucleotide variant
Location: chr11:2884129 (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

Disease context

IMAGe syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDKN1C p.Phe265Ser Likely pathogenic ★ same residue
CDKN1C p.Phe265= Likely benign ★ same residue
CDKN1C p.Arg268Ser Likely pathogenic ★★ same condition
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same condition
CDKN1C c.788-3C>T Uncertain significance ★★ same condition
CDKN1C c.-10-13C>T Uncertain significance ★★ ⚠ same condition
CDKN1C c.-10-7T>C Uncertain significance ★★ ⚠ same condition
CDKN1C c.-8C>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-phe265val (accessed [today's date]).

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