Is CEP104 p.Pro196Ser (c.586C>T) pathogenic?

CEP104 p.Pro196Ser (c.586C>T) is classified Uncertain significance in CEP104 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: ambiguous (0.5137); Very rare (popmax 0.00212%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP104 p.Pro196Ser (c.586C>T)?

CEP104 p.Pro196Ser (c.586C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP104 p.Pro196Ser (c.586C>T) in the general population?

CEP104 p.Pro196Ser (c.586C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about CEP104 p.Pro196Ser (c.586C>T)?

AlphaMissense predicts ambiguous (score 0.5137) — an in-silico prediction, not a clinical call.

CEP104 p.Pro196Ser

c.586C>T · rs949661853 · VCV2278967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5137 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5137	ambiguous
REVEL	0.369	indeterminate
SaProt	LLR -10.22	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.0023 · regional, not allelic
Overall
CADD	26.5	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 0.00212% European (non-Finnish) · 25/1,179,506 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00171% 25/1,460,032 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: CEP104
Protein: p.Pro196Ser
Coding: c.586C>T
MANE Select: NM_014704
dbSNP: rs949661853
Type: single nucleotide variant
Location: chr1:3839757 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB

Full CEP104 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

CEP104 p.Pro196= Benign/Likely benign ★★ same residue
CEP104 p.Ala269Thr Uncertain significance ★★ ⚠ same condition
CEP104 p.Ala499Thr Uncertain significance ★★ ⚠ same condition
CEP104 p.Ala629Val Uncertain significance ★★ same condition
CEP104 p.Arg111Gln Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg299Gln Uncertain significance ★★ ⚠ same condition
CEP104 p.Arg382Gln 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/cep104-p-pro196ser (accessed [today's date]).

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