Is CDKN3 p.Gln166His (c.498A>C) pathogenic?

CDKN3 p.Gln166His (c.498A>C) is classified Uncertain significance in CDKN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.2309); Absent from gnomAD v4.1.

How common is CDKN3 p.Gln166His (c.498A>C) in the general population?

CDKN3 p.Gln166His (c.498A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN3 p.Gln166His (c.498A>C)?

AlphaMissense predicts likely benign (score 0.2309) — an in-silico prediction, not a clinical call.

CDKN3 p.Gln166His

c.498A>C · VCV4224806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2309 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2309	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -8.35	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 6.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 23 kb · p 0.00012 · regional, not allelic
Overall
CADD	19.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN3
Protein: p.Gln166His
Coding: c.498A>C
MANE Select: NM_005192
Type: single nucleotide variant
Location: chr14:54417897 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 91.18 · 2 PDB
Residue 166: the tyrosine-protein phosphatase domain; an α-helix

Full CDKN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN3 p.Ala179Thr Uncertain significance ★ ⚠ same type
CDKN3 p.Arg193Trp Uncertain significance ★ ⚠ same type
CDKN3 p.Asn91Lys Uncertain significance ★ ⚠ same type
CDKN3 p.Glu124Gly Uncertain significance ★ ⚠ same type
CDKN3 p.Glu125Asp Uncertain significance ★ ⚠ same type
CDKN3 p.Ile29Met Uncertain significance ★ ⚠ same type
CDKN3 p.Ile75Met Uncertain significance ★ ⚠ same type
CDKN3 p.Ile7Met 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/cdkn3-p-gln166his (accessed [today's date]).

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