Is CENPF p.Ala243Pro (c.727G>C) pathogenic?

CENPF p.Ala243Pro (c.727G>C) is classified Uncertain significance in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.0943); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CENPF p.Ala243Pro (c.727G>C)?

CENPF p.Ala243Pro (c.727G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CENPF p.Ala243Pro (c.727G>C) in the general population?

CENPF p.Ala243Pro (c.727G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CENPF p.Ala243Pro (c.727G>C)?

AlphaMissense predicts likely benign (score 0.0943) — an in-silico prediction, not a clinical call.

CENPF p.Ala243Pro

c.727G>C · VCV4000440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0943	likely benign
REVEL	0.186	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 -1.7, phastCons 0.39
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	19.05	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 0.00167% Admixed American · 1/59,988 alleles

Overall 0.00131% 2/152,134 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,988
African / African-American	0.00133%	74,914

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.Ala243Pro
Coding: c.727G>C
MANE Select: NM_016343
Type: single nucleotide variant
Location: chr1:214620808 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 243: 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-ala243pro (accessed [today's date]).

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