Is CEP104 p.Lys693Glu (c.2077A>G) pathogenic?

CEP104 p.Lys693Glu (c.2077A>G) is classified Uncertain significance in CEP104 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-26). AlphaMissense: likely benign (0.1207); Rare (popmax 0.116%, mid); Associated with Inborn genetic diseases.

What condition is associated with CEP104 p.Lys693Glu (c.2077A>G)?

CEP104 p.Lys693Glu (c.2077A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP104 p.Lys693Glu (c.2077A>G) in the general population?

CEP104 p.Lys693Glu (c.2077A>G) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about CEP104 p.Lys693Glu (c.2077A>G)?

AlphaMissense predicts likely benign (score 0.1207) — an in-silico prediction, not a clinical call.

CEP104 p.Lys693Glu

c.2077A>G · VCV3490441

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1207 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1207	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.0023 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% Middle Eastern · 7/6,060 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00168% 27/1,608,490 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	866
Remaining individualsnot grpmax-eligible	0.00803%	12,451
African / African-American	0.00134%	74,450
South Asian	0.00112%	89,462
European (non-Finnish)	0.0011%	90,702

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.Lys693Glu
Coding: c.2077A>G
MANE Select: NM_014704
Type: single nucleotide variant
Location: chr1:3829340 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP104 p.Lys693= 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-lys693glu (accessed [today's date]).

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