Is CENPF p.Val2009Ala (c.6026T>C) pathogenic?

CENPF p.Val2009Ala (c.6026T>C) is classified Conflicting classifications of pathogenicity in CENPF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.2521); Ultra-rare (popmax 0.017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CENPF p.Val2009Ala (c.6026T>C)?

CENPF p.Val2009Ala (c.6026T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CENPF p.Val2009Ala (c.6026T>C) in the general population?

CENPF p.Val2009Ala (c.6026T>C) is ultra-rare (popmax 0.017%, nfe) (gnomAD).

What do computational predictors say about CENPF p.Val2009Ala (c.6026T>C)?

AlphaMissense predicts likely benign (score 0.2521) — an in-silico prediction, not a clinical call.

CENPF p.Val2009Ala

c.6026T>C · rs202092147 · VCV1337102

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2521 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2521	likely benign
REVEL	0.045	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 1.6	GERP -0.88, phastCons 0.017
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	12.11	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 0.017% European (non-Finnish) · 201/1,179,984 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.0181% 292/1,613,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.133%	753
European (non-Finnish)grpmax	0.017%	5,871
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00401%	24,948

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val2009Ala
Coding: c.6026T>C
MANE Select: NM_016343
dbSNP: rs202092147
Type: single nucleotide variant
Location: chr1:214645596 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)

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.Val2009Leu Conflicting classifications of pathogenicity ★ ⚠ 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-val2009ala (accessed [today's date]).

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