Is CENPF p.Ala437Pro (c.1309G>C) pathogenic?

CENPF p.Ala437Pro (c.1309G>C) is classified Uncertain significance in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-14). AlphaMissense: likely pathogenic (0.8544); Absent from gnomAD v4.1.

How common is CENPF p.Ala437Pro (c.1309G>C) in the general population?

CENPF p.Ala437Pro (c.1309G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CENPF p.Ala437Pro (c.1309G>C)?

AlphaMissense predicts likely pathogenic (score 0.8544) — an in-silico prediction, not a clinical call.

CENPF p.Ala437Pro

c.1309G>C · rs2528370538 · VCV2123184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8544 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.8544	likely pathogenic · top 2% in CENPF
REVEL	0.37	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CENPF
Protein: p.Ala437Pro
Coding: c.1309G>C
MANE Select: NM_016343
dbSNP: rs2528370538
Type: single nucleotide variant
Location: chr1:214630648 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 437: 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 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
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-ala437pro (accessed [today's date]).

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