Is CEP104 p.Cys54Ser (c.161G>C) pathogenic?

CEP104 p.Cys54Ser (c.161G>C) is classified Uncertain significance in CEP104 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: ambiguous (0.3674); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CEP104 p.Cys54Ser (c.161G>C)?

CEP104 p.Cys54Ser (c.161G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP104 p.Cys54Ser (c.161G>C) in the general population?

CEP104 p.Cys54Ser (c.161G>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CEP104 p.Cys54Ser (c.161G>C)?

AlphaMissense predicts ambiguous (score 0.3674) — an in-silico prediction, not a clinical call.

CEP104 p.Cys54Ser

c.161G>C · VCV4612195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3674 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3674	ambiguous
REVEL	0.351	indeterminate
SaProt	LLR -3.10	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.0023 · regional, not allelic
Overall
CADD	23.7	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00212% 31/1,460,496 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0064%	15,618
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,572
African / African-American	0.00267%	37,477
European (non-Finnish)	0.00186%	53,621
South Asian	0.0011%	90,822

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.Cys54Ser
Coding: c.161G>C
MANE Select: NM_014704
Type: single nucleotide variant
Location: chr1:3848734 (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.Cys54Ter Likely pathogenic ★ 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-cys54ser (accessed [today's date]).

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