Is CENPL p.Arg30Pro (c.89G>C) pathogenic?

CENPL p.Arg30Pro (c.89G>C) is classified Uncertain significance in CENPL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.1695); Ultra-rare (popmax 0.0217%, amr).

How common is CENPL p.Arg30Pro (c.89G>C) in the general population?

CENPL p.Arg30Pro (c.89G>C) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about CENPL p.Arg30Pro (c.89G>C)?

AlphaMissense predicts likely benign (score 0.1695) — an in-silico prediction, not a clinical call.

CENPL p.Arg30Pro

c.89G>C · VCV4225709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1695 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1695	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -7.20	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 0.78	GERP 1.7, phastCons 0.25
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.099 · regional, not allelic
Overall
CADD	19.9	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

Grpmax group 0.0217% Admixed American · 13/59,992 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000806% 13/1,613,900 alleles · ultra-rare

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: CENPL
Protein: p.Arg30Pro
Coding: c.89G>C
MANE Select: NM_001387287
Type: single nucleotide variant
Location: chr1:173811211 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 12 PDB
Residue 30: an α-helix

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

Similar variants

CENPL p.Arg30Gln Uncertain significance ★ ⚠ same residue
CENPL p.Ala108Val Uncertain significance ★ ⚠ same type
CENPL p.Ala212Gly Uncertain significance ★ ⚠ same type
CENPL p.Ala227Thr Uncertain significance ★ ⚠ same type
CENPL p.Ala255Thr Uncertain significance ★ ⚠ same type
CENPL p.Arg16Ile Uncertain significance ★ ⚠ same type
CENPL p.Asn187Lys Uncertain significance ★ ⚠ same type
CENPL p.Asn87Ser 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/cenpl-p-arg30pro (accessed [today's date]).

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