Is CDKN1C p.Ala217Val (c.650C>T) pathogenic?

CDKN1C p.Ala217Val (c.650C>T) is classified Uncertain significance in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). AlphaMissense: likely benign (0.1205); Very rare (popmax 0.00129%, sas); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala217Val (c.650C>T)?

CDKN1C p.Ala217Val (c.650C>T) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala217Val (c.650C>T) in the general population?

CDKN1C p.Ala217Val (c.650C>T) is very rare (popmax 0.00129%, sas) (gnomAD).

What do computational predictors say about CDKN1C p.Ala217Val (c.650C>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

CDKN1C p.Ala217Val

c.650C>T · rs2494384682 · VCV2680541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00129%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -0.66, phastCons 0.98
Overall
CADD	18.52	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A228V vs ClinVar A217V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00129% South Asian · 1/77,662 alleles

Filtering AF 0.000662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00051%

Overall 0.00108% 14/1,296,398 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00129%	77,662
European (non-Finnish)	0.00119%	84,316

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDKN1C
Protein: p.Ala217Val
Coding: c.650C>T
MANE Select: NM_001122630
dbSNP: rs2494384682
Type: single nucleotide variant
Location: chr11:2884807 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 217: the 'disordered' region

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.Ala217Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala217= Likely benign ★ 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

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-ala217val (accessed [today's date]).

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