Is CENPF p.Ala190Asp (c.569C>A) pathogenic?

CENPF p.Ala190Asp (c.569C>A) is classified Uncertain significance in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.2448); Very rare (popmax 9.22e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CENPF p.Ala190Asp (c.569C>A)?

CENPF p.Ala190Asp (c.569C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CENPF p.Ala190Asp (c.569C>A) in the general population?

CENPF p.Ala190Asp (c.569C>A) is very rare (popmax 9.22e-05%, nfe) (gnomAD).

What do computational predictors say about CENPF p.Ala190Asp (c.569C>A)?

AlphaMissense predicts likely benign (score 0.2448) — an in-silico prediction, not a clinical call.

CENPF p.Ala190Asp

c.569C>A · VCV4834693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2448 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.22e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2448	likely benign
REVEL	0.114	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.56 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1	GERP 1.7, phastCons 0.22
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	23.4	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 9.22e-05% European (non-Finnish) · 1/1,084,936 alleles

Overall 7.42e-05% 1/1,347,376 alleles · very rare

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.Ala190Asp
Coding: c.569C>A
MANE Select: NM_016343
Type: single nucleotide variant
Location: chr1:214619216 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 190: 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

Disease context

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

Similar variants

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
CENPF p.Arg178Gln 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-ala190asp (accessed [today's date]).

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