Is CENPF p.Ser2072Pro (c.6214T>C) pathogenic?

CENPF p.Ser2072Pro (c.6214T>C) is classified Conflicting classifications of pathogenicity in CENPF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-20). AlphaMissense: likely pathogenic (0.6338); Rare (popmax 0.227%, eas); Associated with Stromme syndrome.

What condition is associated with CENPF p.Ser2072Pro (c.6214T>C)?

CENPF p.Ser2072Pro (c.6214T>C) is associated with Stromme syndrome (ClinVar).

How common is CENPF p.Ser2072Pro (c.6214T>C) in the general population?

CENPF p.Ser2072Pro (c.6214T>C) is rare (popmax 0.227%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CENPF p.Ser2072Pro (c.6214T>C)?

AlphaMissense predicts likely pathogenic (score 0.6338) — an in-silico prediction, not a clinical call.

CENPF p.Ser2072Pro

c.6214T>C · rs3748694 · VCV2439896

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6338 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Stromme syndrome

Computational evidence

Protein change
AlphaMissense	0.6338	likely pathogenic · top 5% in CENPF
REVEL	0.121	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP 0.83, phastCons 0.058
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	19.75	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 0.227% East Asian · 102/44,874 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.178%

Overall 0.00725% 117/1,614,106 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.227%	440
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00167%	60,012
African / African-American	0.00133%	75,016
European (non-Finnish)	0.000847%	118,001

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.Ser2072Pro
Coding: c.6214T>C
MANE Select: NM_016343
dbSNP: rs3748694
Type: single nucleotide variant
Location: chr1:214645784 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 2072: the 'interaction with nde1 and ndel1' region

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

Disease context

Stromme syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CENPF c.1195-2A>G Likely pathogenic ★★ same condition
CENPF c.1323+1G>A Pathogenic ★★ same condition
CENPF p.Arg1667Ter Pathogenic/Likely pathogenic ★★ same condition
CENPF p.Arg2407Ter Pathogenic/Likely pathogenic ★★ same condition
CENPF p.Arg2898Ter Pathogenic ★★ same condition
CENPF p.Arg3094Ter Likely pathogenic ★★ same condition
CENPF p.Glu1257Ter Pathogenic ★★ same condition
CENPF p.Glu582Ter Pathogenic ★★ 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-ser2072pro (accessed [today's date]).

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