Is CENPC p.Pro876Thr (c.2626C>A) pathogenic?

CENPC p.Pro876Thr (c.2626C>A) is classified Uncertain significance in CENPC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely pathogenic (0.6388); Absent from gnomAD v4.1.

How common is CENPC p.Pro876Thr (c.2626C>A) in the general population?

CENPC p.Pro876Thr (c.2626C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CENPC p.Pro876Thr (c.2626C>A)?

AlphaMissense predicts likely pathogenic (score 0.6388) — an in-silico prediction, not a clinical call.

CENPC p.Pro876Thr

c.2626C>A · VCV3831501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6388 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6388	likely pathogenic · top 9% in CENPC
REVEL	0.298	indeterminate
SaProt	LLR -10.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 73 kb · p 0.0018 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CENPC
Protein: p.Pro876Thr
Coding: c.2626C>A
MANE Select: NM_001812
Type: single nucleotide variant
Location: chr4:67490011 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.33 · 17 PDB

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

Similar variants

CENPC p.Ala165Thr Uncertain significance ★ ⚠ same type
CENPC p.Ala23Val Uncertain significance ★ ⚠ same type
CENPC p.Ala313Val Uncertain significance ★ ⚠ same type
CENPC p.Ala324Thr Uncertain significance ★ ⚠ same type
CENPC p.Ala783Glu Uncertain significance ★ ⚠ same type
CENPC p.Ala783Thr Uncertain significance ★ ⚠ same type
CENPC p.Arg24His Uncertain significance ★ ⚠ same type
CENPC p.Arg272Gln 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/cenpc-p-pro876thr (accessed [today's date]).

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