Is CEP104 p.Lys693= (c.2079A>G) pathogenic?

CEP104 p.Lys693= (c.2079A>G) is classified Likely benign in CEP104 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). Very rare (popmax 0.000254%, nfe).

How common is CEP104 p.Lys693= (c.2079A>G) in the general population?

CEP104 p.Lys693= (c.2079A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

CEP104 p.Lys693=

c.2079A>G · VCV4905437

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.5
Overall
CADD	2.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,178,994 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000249% 4/1,607,908 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,246
European (non-Finnish)grpmax	0.000254%	392,998

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys693=
Coding: c.2079A>G
MANE Select: NM_014704
Type: single nucleotide variant
Location: chr1:3829338 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB
Residue 693: a UniProt-annotated variant site (in mrt77)

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

Similar variants

CEP104 p.Lys693Glu Uncertain significance ★★ ⚠ same residue
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.Arg631Ter 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

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-lys693 (accessed [today's date]).

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