Is CEP104 p.Cys101Arg (c.301T>C) pathogenic?

CEP104 p.Cys101Arg (c.301T>C) is classified Uncertain significance in CEP104 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: ambiguous (0.5467); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEP104 p.Cys101Arg (c.301T>C)?

CEP104 p.Cys101Arg (c.301T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP104 p.Cys101Arg (c.301T>C) in the general population?

CEP104 p.Cys101Arg (c.301T>C) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about CEP104 p.Cys101Arg (c.301T>C)?

AlphaMissense predicts ambiguous (score 0.5467) — an in-silico prediction, not a clinical call.

CEP104 p.Cys101Arg

c.301T>C · rs548106670 · VCV2222652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5467 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5467	ambiguous
REVEL	0.442	indeterminate
SaProt	LLR -11.35	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.0023 · regional, not allelic
Overall
CADD	24.1	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 0.0133% African / African-American · 10/75,064 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.000619% 10/1,614,206 alleles · ultra-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.Cys101Arg
Coding: c.301T>C
MANE Select: NM_014704
dbSNP: rs548106670
Type: single nucleotide variant
Location: chr1:3847600 (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.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
CEP104 p.Arg388His 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-cys101arg (accessed [today's date]).

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