Is CCNQ p.His159Arg (c.476A>G) pathogenic?

CCNQ p.His159Arg (c.476A>G) is classified Uncertain significance in CCNQ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-09). AlphaMissense: likely benign (0.2845); Very rare (popmax 0.000112%, nfe).

How common is CCNQ p.His159Arg (c.476A>G) in the general population?

CCNQ p.His159Arg (c.476A>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about CCNQ p.His159Arg (c.476A>G)?

AlphaMissense predicts likely benign (score 0.2845) — an in-silico prediction, not a clinical call.

CCNQ p.His159Arg

c.476A>G · VCV4718429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2845	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -4.08	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 5.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 11 kb · p 2.8e-07 · regional, not allelic
Overall
CADD	21.1	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

Grpmax group 0.000112% European (non-Finnish) · 1/895,100 alleles

Overall 9.12e-05% 1/1,097,057 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: CCNQ
Protein: p.His159Arg
Coding: c.476A>G
MANE Select: NM_152274
Type: single nucleotide variant
Location: chrX:153592687 (GRCh38)
Structure: AlphaFold pLDDT 88.81

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

Similar variants

CCNQ c.113-85T>C Benign ★★ same type
CCNQ c.296+72C>T Benign ★★ same type
CCNQ c.297-320A>G Benign ★★ same type
CCNQ c.429+171C>T Benign ★★ same type
CCNQ c.429+8C>T Benign ★★ same type
CCNQ c.430-12G>A Benign/Likely benign ★★ same type
CCNQ c.657+144C>T Benign ★★ same type
CCNQ p.Ala209= Benign/Likely benign ★★ 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/ccnq-p-his159arg (accessed [today's date]).

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