Is CENPP p.Asp55Glu (c.165T>A) pathogenic?

CENPP p.Asp55Glu (c.165T>A) is classified Uncertain significance in CENPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.241); Absent from gnomAD v4.1.

How common is CENPP p.Asp55Glu (c.165T>A) in the general population?

CENPP p.Asp55Glu (c.165T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CENPP p.Asp55Glu (c.165T>A)?

AlphaMissense predicts likely benign (score 0.241) — an in-silico prediction, not a clinical call.

CENPP p.Asp55Glu

c.165T>A · VCV4834881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.241 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.241	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.21	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 0.043	GERP -0.25, phastCons 0.34
Regional constraint	o/e 0.96	unconstrained · MANE · 287 kb · p 0.47 · regional, not allelic
Overall
CADD	20.9	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: CENPP
Protein: p.Asp55Glu
Coding: c.165T>A
MANE Select: NM_001012267
Type: single nucleotide variant
Location: chr9:92332227 (GRCh38)
Gene constraint: LOEUF 1.272 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.96 · 13 PDB
Residue 55: an α-helix

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

Similar variants

CENPP p.Cys283Ter Likely pathogenic ★ same type
CENPP p.Ala17Val Uncertain significance ★ ⚠ same type
CENPP p.Ala211Thr Uncertain significance ★ ⚠ same type
CENPP p.Ala258Gly Uncertain significance ★ ⚠ same type
CENPP p.Arg180His Uncertain significance ★ ⚠ same type
CENPP p.Arg209Cys Uncertain significance ★ ⚠ same type
CENPP p.Arg209Gly Uncertain significance ★ ⚠ same type
CENPP p.Arg209His 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/cenpp-p-asp55glu (accessed [today's date]).

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