Is CEP76 p.Pro103Ser (c.307C>T) pathogenic?

CEP76 p.Pro103Ser (c.307C>T) is classified Pathogenic in CEP76 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely benign (0.3212); Absent from gnomAD v4.1; Associated with Joubert syndrome 1.

What condition is associated with CEP76 p.Pro103Ser (c.307C>T)?

CEP76 p.Pro103Ser (c.307C>T) is associated with Joubert syndrome 1 (ClinVar).

How common is CEP76 p.Pro103Ser (c.307C>T) in the general population?

CEP76 p.Pro103Ser (c.307C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP76 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.3212) — an in-silico prediction, not a clinical call.

CEP76 p.Pro103Ser

c.307C>T · VCV4075828

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3212 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Joubert syndrome 1

Computational evidence

Protein change
AlphaMissense	0.3212	likely benign ⚠ discordant with ClinVar
REVEL	0.42	indeterminate
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 29 kb · p 0.00019 · regional, not allelic
Overall
CADD	23.8	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: CEP76
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_024899
Type: single nucleotide variant
Location: chr18:12699192 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18

Full CEP76 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP76 p.Arg568Pro Likely pathogenic ★ same condition
CEP76 p.Lys374= Pathogenic ★ same condition
CEP76 p.Val24Asp Likely pathogenic ★ same condition
CEP76 p.His301fs Likely pathogenic ★ same condition
CEP76 p.Cys478Arg Likely pathogenic ★ same type
CEP76 p.Ile101Thr Likely pathogenic ★ ⚠ same type
CEP76 p.Leu166Pro Likely pathogenic ★ same type
CEP76 p.Val265Met 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/cep76-p-pro103ser (accessed [today's date]).

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