Is CENPF p.Arg751Trp (c.2251C>T) pathogenic?

CENPF p.Arg751Trp (c.2251C>T) is classified Uncertain significance in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely benign (0.1029); Very rare (popmax 0.00602%, nfe).

How common is CENPF p.Arg751Trp (c.2251C>T) in the general population?

CENPF p.Arg751Trp (c.2251C>T) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about CENPF p.Arg751Trp (c.2251C>T)?

AlphaMissense predicts likely benign (score 0.1029) — an in-silico prediction, not a clinical call.

CENPF p.Arg751Trp

c.2251C>T · rs199832648 · VCV2196051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1029	likely benign
REVEL	0.113	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 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	26.9	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 0.00602% European (non-Finnish) · 71/1,179,940 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00477% 77/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,619
Finnishnot grpmax-eligible	0.00312%	32,009
African / African-American	0.00267%	37,520
East Asian	0.00223%	44,876
Admixed American	0.00167%	59,998

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.Arg751Trp
Coding: c.2251C>T
MANE Select: NM_016343
dbSNP: rs199832648
Type: single nucleotide variant
Location: chr1:214640589 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)

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

Similar variants

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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
CENPF p.Glu361Ter Likely 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-arg751trp (accessed [today's date]).

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