Is CDKN1C p.Arg90His (c.269G>A) pathogenic?

CDKN1C p.Arg90His (c.269G>A) is classified Uncertain significance in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). AlphaMissense: likely pathogenic (0.7807); Absent from gnomAD v4.1.

How common is CDKN1C p.Arg90His (c.269G>A) in the general population?

CDKN1C p.Arg90His (c.269G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN1C p.Arg90His (c.269G>A)?

AlphaMissense predicts likely pathogenic (score 0.7807) — an in-silico prediction, not a clinical call.

CDKN1C p.Arg90His

c.269G>A · VCV4910365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7807 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,533,104)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7807	likely pathogenic
REVEL	0.557	indeterminate
SaProt	LLR -8.24	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 6.9	GERP 0.95, phastCons 1
Overall
CADD	28.7	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 R101H vs ClinVar R90H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,533,104). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKN1C
Protein: p.Arg90His
Coding: c.269G>A
MANE Select: NM_001122630
Type: single nucleotide variant
Location: chr11:2885188 (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

Similar variants

CDKN1C p.Arg90Cys Uncertain significance ★ ⚠ same residue
CDKN1C p.Arg90= Likely benign ★ same residue
CDKN1C p.Arg268Ser Likely pathogenic ★★ ⚠ same type
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same type
CDKN1C p.Cys19Ter Pathogenic/Likely pathogenic ★★ same type
CDKN1C p.Gln219Ter Pathogenic ★★ same type
CDKN1C p.Gln221Ter Pathogenic ★★ same type
CDKN1C p.Gln230Ter Pathogenic ★★ same type

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-arg90his (accessed [today's date]).

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