Is CDKN1C p.Ala78Val (c.233C>T) pathogenic?

CDKN1C p.Ala78Val (c.233C>T) is classified Uncertain significance in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-18). AlphaMissense: likely pathogenic (0.5729); Absent from gnomAD v4.1; Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala78Val (c.233C>T)?

CDKN1C p.Ala78Val (c.233C>T) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala78Val (c.233C>T) in the general population?

CDKN1C p.Ala78Val (c.233C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN1C p.Ala78Val (c.233C>T)?

AlphaMissense predicts likely pathogenic (score 0.5729) — an in-silico prediction, not a clinical call.

CDKN1C p.Ala78Val

c.233C>T · rs1848969930 · VCV943653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5729 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,548,658)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.5729	likely pathogenic
REVEL	0.196	benign-leaning
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP -1.7, phastCons 1
Overall
CADD	21.7	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 A89V vs ClinVar A78V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,548,658). 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.Ala78Val
Coding: c.233C>T
MANE Select: NM_001122630
dbSNP: rs1848969930
Type: single nucleotide variant
Location: chr11:2885224 (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

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

Similar variants

CDKN1C p.Ala78Thr Uncertain significance ★★ ⚠ same residue
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same condition
CDKN1C p.Cys19Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1C p.Gln219Ter Pathogenic ★★ same condition
CDKN1C p.Gln221Ter Pathogenic ★★ same condition
CDKN1C p.Gln230Ter Pathogenic ★★ same condition
CDKN1C p.Glu119Ter Pathogenic ★★ same condition
CDKN1C p.Glu214Ter 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/cdkn1c-p-ala78val (accessed [today's date]).

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