Is CDKN1C p.Gln85Arg (c.254A>G) pathogenic?

CDKN1C p.Gln85Arg (c.254A>G) is classified Uncertain significance in CDKN1C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-02). AlphaMissense: likely pathogenic (0.868); Very rare (popmax 0.00137%, afr); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Gln85Arg (c.254A>G)?

CDKN1C p.Gln85Arg (c.254A>G) is associated with Beckwith-Wiedemann syndrome, IMAGe syndrome (ClinVar).

How common is CDKN1C p.Gln85Arg (c.254A>G) in the general population?

CDKN1C p.Gln85Arg (c.254A>G) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about CDKN1C p.Gln85Arg (c.254A>G)?

AlphaMissense predicts likely pathogenic (score 0.868) — an in-silico prediction, not a clinical call.

CDKN1C p.Gln85Arg

c.254A>G · rs1220704341 · VCV1056491

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.868 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.868	likely pathogenic
REVEL	0.331	indeterminate
SaProt	LLR -8.10	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP -0.071, phastCons 1
Overall
CADD	25.1	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 Q96R vs ClinVar Q85R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,202 alleles

Overall 7.19e-05% 1/1,390,266 alleles · very rare

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.Gln85Arg
Coding: c.254A>G
MANE Select: NM_001122630
dbSNP: rs1220704341
Type: single nucleotide variant
Location: chr11:2885203 (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

Also linked: IMAGe syndrome

Similar variants

CDKN1C p.Gln85His Uncertain significance ★ ⚠ same residue
CDKN1C p.Gln85= 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
CDKN1C p.Gln230Ter 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-gln85arg (accessed [today's date]).

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