Is CEP55 p.Ser2Phe (c.5C>T) pathogenic?

CEP55 p.Ser2Phe (c.5C>T) is classified Uncertain significance in CEP55 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-06). AlphaMissense: likely benign (0.2002); Very rare (popmax 0.00442%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP55 p.Ser2Phe (c.5C>T)?

CEP55 p.Ser2Phe (c.5C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP55 p.Ser2Phe (c.5C>T) in the general population?

CEP55 p.Ser2Phe (c.5C>T) is very rare (popmax 0.00442%, nfe) (gnomAD).

What do computational predictors say about CEP55 p.Ser2Phe (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2002) — an in-silico prediction, not a clinical call.

CEP55 p.Ser2Phe

c.5C>T · rs1012047533 · VCV2482790

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00442%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2002	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 28 kb · p 0.0058 · regional, not allelic
Overall
CADD	25.0	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 0.00442% European (non-Finnish) · 52/1,175,436 alleles

Filtering AF 0.00344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00311%

Overall 0.00325% 52/1,601,462 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: CEP55
Protein: p.Ser2Phe
Coding: c.5C>T
MANE Select: NM_018131
dbSNP: rs1012047533
Type: single nucleotide variant
Location: chr10:93500056 (GRCh38)
Gene constraint: LOEUF 1.138 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 4 PDB
Residue 2: the 'disordered' region

Full CEP55 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

CEP55 p.Arg86Ter Pathogenic ★★ same condition
CEP55 p.Arg385Gln Uncertain significance ★★ ⚠ same condition
CEP55 p.His293Arg Uncertain significance ★★ ⚠ same condition
CEP55 p.Val379Ala Uncertain significance ★★ ⚠ same condition
CEP55 c.1191+2T>C Pathogenic ★ same condition
CEP55 p.Ala242Ser Uncertain significance ★ ⚠ same condition
CEP55 p.Ala358Glu Uncertain significance ★ ⚠ same condition
CEP55 p.Ala424Thr 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/cep55-p-ser2phe (accessed [today's date]).

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