Is CENPI p.Trp100Arg (c.298T>C) pathogenic?

CENPI p.Trp100Arg (c.298T>C) is classified Uncertain significance in CENPI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: ambiguous (0.4515); Very rare (popmax 0.00666%, amr).

How common is CENPI p.Trp100Arg (c.298T>C) in the general population?

CENPI p.Trp100Arg (c.298T>C) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about CENPI p.Trp100Arg (c.298T>C)?

AlphaMissense predicts ambiguous (score 0.4515) — an in-silico prediction, not a clinical call.

CENPI p.Trp100Arg

c.298T>C · VCV3265914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4515	ambiguous
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.33, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 62 kb · p 9e-05 · regional, not allelic
Overall
CADD	19.52	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

Grpmax group 0.00666% Admixed American · 3/45,060 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000964%

Overall 0.00168% 20/1,188,529 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,020
European (non-Finnish)	0.00194%	51,654

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: CENPI
Protein: p.Trp100Arg
Coding: c.298T>C
MANE Select: NM_001386188
Type: single nucleotide variant
Location: chrX:101102345 (GRCh38)
Structure: AlphaFold pLDDT 74.27 · 12 PDB
Residue 100: an α-helix

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

Similar variants

CENPI p.Val10Ile Benign ★★ same type
CENPI p.Val276Met Benign ★★ same type
CENPI c.1195+6A>G Uncertain significance ★ same type
CENPI c.687+8C>T Uncertain significance ★ same type
CENPI p.Ala147Gly Uncertain significance ★ ⚠ same type
CENPI p.Ala479Val Uncertain significance ★ same type
CENPI p.Ala674Asp Uncertain significance ★ ⚠ same type
CENPI p.Ala692Thr 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/cenpi-p-trp100arg (accessed [today's date]).

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