Is CENPF p.Arg3053Trp (c.9157C>T) pathogenic?

CENPF p.Arg3053Trp (c.9157C>T) is classified Uncertain significance in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely benign (0.0896); Ultra-rare (popmax 0.0293%, afr).

How common is CENPF p.Arg3053Trp (c.9157C>T) in the general population?

CENPF p.Arg3053Trp (c.9157C>T) is ultra-rare (popmax 0.0293%, afr) (gnomAD).

What do computational predictors say about CENPF p.Arg3053Trp (c.9157C>T)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

CENPF p.Arg3053Trp

c.9157C>T · rs140950062 · VCV1523284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0293%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.055	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP 2.2
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	21.5	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 0.0293% African / African-American · 22/75,014 alleles

Filtering AF 0.0198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00997% 161/1,614,042 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0293%	3,410
European (non-Finnish)	0.0109%	9,147
Remaining individualsnot grpmax-eligible	0.008%	12,500
Admixed American	0.005%	20,005
East Asian	0.00223%	44,882
South Asian	0.0011%	91,054

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.Arg3053Trp
Coding: c.9157C>T
MANE Select: NM_016343
dbSNP: rs140950062
Type: single nucleotide variant
Location: chr1:214663606 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 3053: the 'disordered' region

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

Similar variants

CENPF p.Arg3053Gln Uncertain significance ★★ ⚠ same residue
CENPF c.1195-2A>G Likely pathogenic ★★ same type
CENPF c.1323+1G>A Pathogenic ★★ same type
CENPF p.Arg1667Ter Pathogenic/Likely pathogenic ★★ same type
CENPF p.Arg2407Ter Pathogenic/Likely pathogenic ★★ same type
CENPF p.Arg2898Ter Pathogenic ★★ same type
CENPF p.Arg3094Ter Likely pathogenic ★★ same type
CENPF p.Glu1257Ter Pathogenic ★★ 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/cenpf-p-arg3053trp (accessed [today's date]).

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