Is CDKN2C p.Gly103= (c.309G>A) pathogenic?

CDKN2C p.Gly103= (c.309G>A) is classified Likely benign in CDKN2C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). Very rare (popmax 0.000593%, nfe).

How common is CDKN2C p.Gly103= (c.309G>A) in the general population?

CDKN2C p.Gly103= (c.309G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

CDKN2C p.Gly103=

c.309G>A · VCV4533525

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

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 3.2	GERP -0.02, phastCons 1
Overall
CADD	11.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,034 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,070 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: CDKN2C
Protein: p.Gly103=
Coding: c.309G>A
MANE Select: NM_078626
Type: single nucleotide variant
Location: chr1:50974072 (GRCh38)
Gene constraint: LOEUF 0.94 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 6 PDB
Residue 103: a β-strand

Full CDKN2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN2C p.Asn159= Likely benign ★★ same type
CDKN2C p.Ala127Asp Uncertain significance ★ ⚠ same type
CDKN2C p.Ala161Gly Uncertain significance ★ ⚠ same type
CDKN2C p.Ala77Val Uncertain significance ★ ⚠ same type
CDKN2C p.Arg39Ser Uncertain significance ★ ⚠ same type
CDKN2C p.Asp17His Uncertain significance ★ ⚠ same type
CDKN2C p.Asp17Tyr Uncertain significance ★ ⚠ same type
CDKN2C p.Asp64His Uncertain significance ★ ⚠ 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/cdkn2c-p-gly103 (accessed [today's date]).

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