Is CEP85L p.Ser58Cys (c.172A>T) pathogenic?

CEP85L p.Ser58Cys (c.172A>T) is classified Likely pathogenic in CEP85L (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.2683); Absent from gnomAD v4.1; Associated with Posterior Predominant Lissencephaly.

What condition is associated with CEP85L p.Ser58Cys (c.172A>T)?

CEP85L p.Ser58Cys (c.172A>T) is associated with Posterior Predominant Lissencephaly (ClinVar).

How common is CEP85L p.Ser58Cys (c.172A>T) in the general population?

CEP85L p.Ser58Cys (c.172A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP85L p.Ser58Cys (c.172A>T)?

AlphaMissense predicts likely benign (score 0.2683) — an in-silico prediction, not a clinical call.

CEP85L p.Ser58Cys

c.172A>T · rs1774230502 · VCV979032

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2683 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Posterior Predominant Lissencephaly

Computational evidence

Protein change
AlphaMissense	0.2683	likely benign ⚠ discordant with ClinVar
REVEL	0.239	benign-leaning
SaProt	LLR -10.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 43 bp · p 0.00081 · regional, not allelic
Overall
CADD	27.1	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

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.Ser58Cys
Coding: c.172A>T
MANE Select: NM_001042475
dbSNP: rs1774230502
Type: single nucleotide variant
Location: chr6:118632513 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.98
Residue 58: a UniProt-annotated variant site (in lis10); the 'disordered' region

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

Disease context

Posterior Predominant Lissencephaly

Similar variants

CEP85L p.Ser58Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
PLN p.Leu39Ter Pathogenic/Likely pathogenic ★★ same condition
CEP85L p.Gly69Arg Likely pathogenic ★ same condition
CEP85L p.Glu554Ala Uncertain significance ★ ⚠ same condition
CEP85L p.Ser349Arg Uncertain significance ★ ⚠ same condition
PLN p.Thr8Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
CEP85L c.232+3G>T Pathogenic/Likely pathogenic same condition
CEP85L c.232+5G>A Pathogenic/Likely pathogenic 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-ser58cys (accessed [today's date]).

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