Is CENPU p.Arg6Pro (c.17G>C) pathogenic?

CENPU p.Arg6Pro (c.17G>C) is classified Uncertain significance in CENPU (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely benign (0.1545); Rare (popmax 0.227%, eas).

How common is CENPU p.Arg6Pro (c.17G>C) in the general population?

CENPU p.Arg6Pro (c.17G>C) is rare (popmax 0.227%, eas) (gnomAD).

What do computational predictors say about CENPU p.Arg6Pro (c.17G>C)?

AlphaMissense predicts likely benign (score 0.1545) — an in-silico prediction, not a clinical call.

CENPU p.Arg6Pro

c.17G>C · VCV4000511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1545 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1545	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -7.53	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 0.47	GERP -1.4, phastCons 0.002
Regional constraint	o/e 1.04	unconstrained · MANE · 39 kb · p 0.37 · regional, not allelic
Overall
CADD	14.5	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 0.227% East Asian · 96/42,314 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.013% 205/1,573,330 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.227%	441
South Asian	0.118%	851
Remaining individualsnot grpmax-eligible	0.0082%	12,198
European (non-Finnish)	0.000172%	580,794

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: CENPU
Protein: p.Arg6Pro
Coding: c.17G>C
MANE Select: NM_024629
Type: single nucleotide variant
Location: chr4:184734046 (GRCh38)
Gene constraint: LOEUF 1.207 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.09 · 18 PDB
Residue 6: the 'disordered' region

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

Similar variants

CENPU p.Ala115Val Uncertain significance ★ ⚠ same type
CENPU p.Ala169Thr Uncertain significance ★ ⚠ same type
CENPU p.Ala201Ser Uncertain significance ★ ⚠ same type
CENPU p.Ala400Thr Uncertain significance ★ ⚠ same type
CENPU p.Ala79Pro Uncertain significance ★ ⚠ same type
CENPU p.Arg161His Uncertain significance ★ ⚠ same type
CENPU p.Arg19Cys Uncertain significance ★ ⚠ same type
CENPU p.Arg347Thr 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/cenpu-p-arg6pro (accessed [today's date]).

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