Is CCNP p.Cys176Ser (c.527G>C) pathogenic?

CCNP p.Cys176Ser (c.527G>C) is classified Uncertain significance in CCNP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). AlphaMissense: ambiguous (0.4794); Absent from gnomAD v4.1.

How common is CCNP p.Cys176Ser (c.527G>C) in the general population?

CCNP p.Cys176Ser (c.527G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNP p.Cys176Ser (c.527G>C)?

AlphaMissense predicts ambiguous (score 0.4794) — an in-silico prediction, not a clinical call.

CCNP p.Cys176Ser

c.527G>C · VCV3264596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4794 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4794	ambiguous
REVEL	0.186	benign-leaning
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,586 bp · p 0.45 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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: CCNP
Protein: p.Cys176Ser
Coding: c.527G>C
MANE Select: NM_024877
Type: single nucleotide variant
Location: chr19:40223533 (GRCh38)
Gene constraint: LOEUF 1.397 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.87
Residue 176: the cyclin n-terminal domain

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

Similar variants

CCNP p.Ala173Ser Uncertain significance ★ ⚠ same type
CCNP p.Ala186Val Uncertain significance ★ ⚠ same type
CCNP p.Ala243Val Uncertain significance ★ ⚠ same type
CCNP p.Ala265Thr Uncertain significance ★ ⚠ same type
CCNP p.Ala37Ser Uncertain significance ★ ⚠ same type
CCNP p.Ala68Glu Uncertain significance ★ ⚠ same type
CCNP p.Ala81Ser Uncertain significance ★ ⚠ same type
CCNP p.Arg101His 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/ccnp-p-cys176ser (accessed [today's date]).

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