Is CENPF p.Arg402Cys (c.1204C>T) pathogenic?

CENPF p.Arg402Cys (c.1204C>T) is classified Likely benign in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). AlphaMissense: likely benign (0.08); Very rare (popmax 0.00549%, sas).

How common is CENPF p.Arg402Cys (c.1204C>T) in the general population?

CENPF p.Arg402Cys (c.1204C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about CENPF p.Arg402Cys (c.1204C>T)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

CENPF p.Arg402Cys

c.1204C>T · VCV4822210

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.31	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -0.68
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	17.62	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 0.00549% South Asian · 5/91,068 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000991% 16/1,613,938 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,214
East Asian	0.00223%	44,880
Admixed American	0.00167%	60,006
African / African-American	0.00134%	74,882
European (non-Finnish)	0.000678%	147,497

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.Arg402Cys
Coding: c.1204C>T
MANE Select: NM_016343
Type: single nucleotide variant
Location: chr1:214630543 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 402: the 'interaction with snap25 and required for localization to the cytoplasm' region

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

Similar variants

CENPF p.Arg402His 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-arg402cys (accessed [today's date]).

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