Is CCNP p.Pro293Ser (c.877C>T) pathogenic?

CCNP p.Pro293Ser (c.877C>T) is classified Uncertain significance in CCNP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely benign (0.0976); Absent from gnomAD v4.1.

How common is CCNP p.Pro293Ser (c.877C>T) in the general population?

CCNP p.Pro293Ser (c.877C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNP p.Pro293Ser (c.877C>T)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

CCNP p.Pro293Ser

c.877C>T · VCV3487495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.93	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 0.23	GERP -3
Regional constraint	o/e 1.04	unconstrained · MANE · 3,586 bp · p 0.45 · regional, not allelic
Overall
CADD	14.62	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: CCNP
Protein: p.Pro293Ser
Coding: c.877C>T
MANE Select: NM_024877
Type: single nucleotide variant
Location: chr19:40223099 (GRCh38)
Gene constraint: LOEUF 1.397 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.87

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

Similar variants

CCNP p.Pro293Arg Uncertain significance ★ ⚠ same residue
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

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-pro293ser (accessed [today's date]).

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