Is CDKN1C p.Ala172= (c.516C>T) pathogenic?

CDKN1C p.Ala172= (c.516C>T) is classified Likely benign in CDKN1C (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-13). Very rare (popmax 0.00176%, afr); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala172= (c.516C>T)?

CDKN1C p.Ala172= (c.516C>T) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala172= (c.516C>T) in the general population?

CDKN1C p.Ala172= (c.516C>T) is very rare (popmax 0.00176%, afr) (gnomAD).

CDKN1C p.Ala172=

c.516C>T · rs1462682672 · VCV1108343

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00176%, afr)

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -0.9
Overall
CADD	6.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% African / African-American · 1/56,804 alleles

Filtering AF 0.000188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000619% 6/969,010 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00176%	56,804
European (non-Finnish)	0.000643%	155,518

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.Ala172=
Coding: c.516C>T
MANE Select: NM_001122630
dbSNP: rs1462682672
Type: single nucleotide variant
Location: chr11:2884941 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 172: the '9 x 4 aa repeats of p-a-p-a' region; a UniProt-annotated variant site (in several cancers)

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.Ala172Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala172Val 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

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-ala172 (accessed [today's date]).

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