Is CEP76 p.Val24Asp (c.71T>A) pathogenic?

CEP76 p.Val24Asp (c.71T>A) is classified Likely pathogenic in CEP76 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely pathogenic (0.9792); Absent from gnomAD v4.1; Associated with Joubert syndrome 1.

What condition is associated with CEP76 p.Val24Asp (c.71T>A)?

CEP76 p.Val24Asp (c.71T>A) is associated with Joubert syndrome 1 (ClinVar).

How common is CEP76 p.Val24Asp (c.71T>A) in the general population?

CEP76 p.Val24Asp (c.71T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP76 p.Val24Asp (c.71T>A)?

AlphaMissense predicts likely pathogenic (score 0.9792) — an in-silico prediction, not a clinical call.

CEP76 p.Val24Asp

c.71T>A · VCV4075832

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9792 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 1

Computational evidence

Protein change
AlphaMissense	0.9792	likely pathogenic ✓ concordant with ClinVar · top 10% in CEP76
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -13.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 29 kb · p 0.00019 · regional, not allelic
Overall
CADD	26.9	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.Val24Asp
Coding: c.71T>A
MANE Select: NM_024899
Type: single nucleotide variant
Location: chr18:12701106 (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.Val24Ala Uncertain significance ★ ⚠ same residue
CEP76 p.Arg568Pro Likely pathogenic ★ same condition
CEP76 p.Lys374= Pathogenic ★ same condition
CEP76 p.Pro103Ser 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

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-val24asp (accessed [today's date]).

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