Is CENPF p.Arg3003Gln (c.9008G>A) pathogenic?

CENPF p.Arg3003Gln (c.9008G>A) is classified Uncertain significance in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-06). AlphaMissense: ambiguous (0.5634); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with CENPF p.Arg3003Gln (c.9008G>A)?

CENPF p.Arg3003Gln (c.9008G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CENPF p.Arg3003Gln (c.9008G>A) in the general population?

CENPF p.Arg3003Gln (c.9008G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CENPF p.Arg3003Gln (c.9008G>A)?

AlphaMissense predicts ambiguous (score 0.5634) — an in-silico prediction, not a clinical call.

CENPF p.Arg3003Gln

c.9008G>A · VCV3490324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5634	ambiguous · top 6% in CENPF
REVEL	0.267	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	29.8	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 0.00534% African / African-American · 4/74,850 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000496% 8/1,613,890 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
European (non-Finnish)	0.000339%	294,993

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: CENPF
Protein: p.Arg3003Gln
Coding: c.9008G>A
MANE Select: NM_016343
Type: single nucleotide variant
Location: chr1:214658895 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 3003: the 'sufficient for centromere localization' region; the 'sufficient for nuclear localization' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CENPF p.Arg3003= Uncertain significance ★★ same residue
CENPF p.Ala1268Val Uncertain significance ★★ ⚠ same condition
CENPF p.Ala1626Val Uncertain significance ★★ ⚠ same condition
CENPF p.Ala1714Thr Uncertain significance ★★ ⚠ same condition
CENPF p.Ala212Asp Uncertain significance ★★ same condition
CENPF p.Ala2616Val Uncertain significance ★★ ⚠ same condition
CENPF p.Arg1325Lys Uncertain significance ★★ ⚠ same condition
CENPF p.Arg1653Trp Uncertain significance ★★ ⚠ same condition

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/cenpf-p-arg3003gln (accessed [today's date]).

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