Is CENPM p.Arg86Pro (c.257G>C) pathogenic?

CENPM p.Arg86Pro (c.257G>C) is classified Uncertain significance in CENPM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.1422); Absent from gnomAD v4.1.

How common is CENPM p.Arg86Pro (c.257G>C) in the general population?

CENPM p.Arg86Pro (c.257G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CENPM p.Arg86Pro (c.257G>C)?

AlphaMissense predicts likely benign (score 0.1422) — an in-silico prediction, not a clinical call.

CENPM p.Arg86Pro

c.257G>C · VCV4000473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1422 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1422	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -11.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.6	GERP -5.4
Regional constraint	o/e 1.05	unconstrained · MANE · 8,017 bp · p 0.48 · regional, not allelic
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

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: CENPM
Protein: p.Arg86Pro
Coding: c.257G>C
MANE Select: NM_024053
Type: single nucleotide variant
Location: chr22:41945278 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.38 · 14 PDB

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

Similar variants

CENPM p.Ala16Asp Uncertain significance ★ ⚠ same type
CENPM p.Arg106Trp Uncertain significance ★ ⚠ same type
CENPM p.Arg114Trp Uncertain significance ★ ⚠ same type
CENPM p.Arg145His Uncertain significance ★ ⚠ same type
CENPM p.Arg148His Uncertain significance ★ ⚠ same type
CENPM p.Asn14Ser Uncertain significance ★ ⚠ same type
CENPM p.Cys131Ser Uncertain significance ★ ⚠ same type
CENPM p.Cys131Tyr 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/cenpm-p-arg86pro (accessed [today's date]).

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