Is CEP104 p.Arg631Ter (c.1891C>T) pathogenic?

CEP104 p.Arg631Ter (c.1891C>T) is classified Pathogenic/Likely pathogenic in CEP104 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-08-01). Very rare (popmax 0.000339%, nfe).

How common is CEP104 p.Arg631Ter (c.1891C>T) in the general population?

CEP104 p.Arg631Ter (c.1891C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

CEP104 p.Arg631Ter

c.1891C>T · rs1644169357 · VCV872689

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.6	GERP -2.6
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,034 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,878 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.Arg631Ter
Coding: c.1891C>T
MANE Select: NM_014704
dbSNP: rs1644169357
Type: single nucleotide variant
Location: chr1:3829943 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB
Residue 631: a UniProt-annotated variant site (in mrt77); an α-helix

Full CEP104 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP104 c.2364+1G>A Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Arg55Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Glu627Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Lys270Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Tyr253Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 c.1120-5T>A Uncertain significance ★★ same type
CEP104 p.Ala269Thr Uncertain significance ★★ ⚠ same type

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-arg631ter (accessed [today's date]).

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