Is CDKN1C p.Ala170Asp (c.509C>A) pathogenic?

CDKN1C p.Ala170Asp (c.509C>A) is classified Uncertain significance in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-15). AlphaMissense: ambiguous (0.4254); Very rare (popmax 0.00435%, eas); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala170Asp (c.509C>A)?

CDKN1C p.Ala170Asp (c.509C>A) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala170Asp (c.509C>A) in the general population?

CDKN1C p.Ala170Asp (c.509C>A) is very rare (popmax 0.00435%, eas) (gnomAD).

What do computational predictors say about CDKN1C p.Ala170Asp (c.509C>A)?

AlphaMissense predicts ambiguous (score 0.4254) — an in-silico prediction, not a clinical call.

CDKN1C p.Ala170Asp

c.509C>A · rs1332953428 · VCV841190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.4254	ambiguous
REVEL	0.016	strongly benign-leaning
SaProt	LLR -11.65	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -0.91
Overall
CADD	8.432	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 A181D vs ClinVar A170D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00435% East Asian · 1/22,982 alleles

Filtering AF 4.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5e-05%

Overall 0.000347% 3/864,836 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00435%	22,982
European (non-Finnish)	0.000247%	405,449

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.Ala170Asp
Coding: c.509C>A
MANE Select: NM_001122630
dbSNP: rs1332953428
Type: single nucleotide variant
Location: chr11:2884948 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 170: the '9 x 4 aa repeats of p-a-p-a' 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.Ala170= Likely benign ★★ same residue
CDKN1C p.Ala170Gly Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala170Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala170Val 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

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-ala170asp (accessed [today's date]).

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