Is CEP85L p.Gln697Ter (c.2089C>T) pathogenic?

CEP85L p.Gln697Ter (c.2089C>T) is classified Likely pathogenic in CEP85L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). Absent from gnomAD v4.1; Associated with lissencephaly 10.

What condition is associated with CEP85L p.Gln697Ter (c.2089C>T)?

CEP85L p.Gln697Ter (c.2089C>T) is associated with lissencephaly 10 (ClinVar).

How common is CEP85L p.Gln697Ter (c.2089C>T) in the general population?

CEP85L p.Gln697Ter (c.2089C>T) is absent from gnomAD v4.1 (gnomAD).

CEP85L p.Gln697Ter

c.2089C>T · rs2533741192 · VCV3064370

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

lissencephaly 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	Δ0.65	donor gain · deltas
Pangolin	Δ0.47	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.6	GERP 1.8, phastCons 1
Overall
CADD	39.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP85L
Protein: p.Gln697Ter
Coding: c.2089C>T
MANE Select: NM_001042475
dbSNP: rs2533741192
Type: single nucleotide variant
Location: chr6:118469237 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.98

Full CEP85L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lissencephaly 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP85L p.Arg151Gln Uncertain significance ★★ ⚠ same condition
CEP85L p.Ile508Val Uncertain significance ★★ ⚠ same condition
CEP85L c.1020+17269T>G Benign ★★ same condition
CEP85L c.1020+17468G>A Likely benign ★★ same condition
CEP85L c.232+5G>C Likely pathogenic ★ same condition
CEP85L p.Asp65Asn Likely pathogenic ★ ⚠ same condition
CEP85L c.1590+3A>T Uncertain significance ★ same condition
CEP85L p.Arg305Trp 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/cep85l-p-gln697ter (accessed [today's date]).

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