Is CDKN1C p.Pro107Leu (c.320C>T) pathogenic?

CDKN1C p.Pro107Leu (c.320C>T) is classified Benign/Likely benign in CDKN1C (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1184); Very rare (popmax 0.00265%, nfe); Associated with Beckwith-Wiedemann syndrome due to CDKN1C mutation.

What condition is associated with CDKN1C p.Pro107Leu (c.320C>T)?

CDKN1C p.Pro107Leu (c.320C>T) is associated with Beckwith-Wiedemann syndrome due to CDKN1C mutation, Beckwith-Wiedemann syndrome, IMAGe syndrome (ClinVar).

How common is CDKN1C p.Pro107Leu (c.320C>T) in the general population?

CDKN1C p.Pro107Leu (c.320C>T) is very rare (popmax 0.00265%, nfe) (gnomAD).

What do computational predictors say about CDKN1C p.Pro107Leu (c.320C>T)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

CDKN1C p.Pro107Leu

c.320C>T · rs771731330 · VCV404254

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00265%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Beckwith-Wiedemann syndrome due to CDKN1C mutation

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -7.53	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 3.1	GERP -0.38, phastCons 1
Overall
CADD	21.1	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 P118L vs ClinVar P107L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00265% European (non-Finnish) · 30/1,132,064 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00163%

Overall 0.00574% 86/1,497,220 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.184%	544
Remaining individualsnot grpmax-eligible	0.012%	8,314
European (non-Finnish)grpmax	0.00265%	37,735
Admixed American	0.00221%	45,192

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro107Leu
Coding: c.320C>T
MANE Select: NM_001122630
dbSNP: rs771731330
Type: single nucleotide variant
Location: chr11:2885137 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 107: a modified residue (omega-n-methylarginine)

Full CDKN1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Beckwith-Wiedemann syndrome due to CDKN1C mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Beckwith-Wiedemann syndrome IMAGe syndrome

Similar variants

CDKN1C p.Pro107Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1C p.Pro107Ser Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro107= Likely benign ★ same residue
CDKN1C p.Arg268Ser Likely pathogenic ★★ same condition
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-pro107leu (accessed [today's date]).

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