Is CEP76 p.Val324Phe (c.970G>T) pathogenic?

CEP76 p.Val324Phe (c.970G>T) is classified Uncertain significance in CEP76 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely pathogenic (0.8432); Absent from gnomAD v4.1.

How common is CEP76 p.Val324Phe (c.970G>T) in the general population?

CEP76 p.Val324Phe (c.970G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP76 p.Val324Phe (c.970G>T)?

AlphaMissense predicts likely pathogenic (score 0.8432) — an in-silico prediction, not a clinical call.

CEP76 p.Val324Phe

c.970G>T · VCV4001162

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8432 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8432	likely pathogenic
REVEL	0.682	pathogenic-leaning
SaProt	LLR -14.08	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 2.7	GERP -1.3, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 29 kb · p 0.00019 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Val324Phe
Coding: c.970G>T
MANE Select: NM_024899
Type: single nucleotide variant
Location: chr18:12686414 (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

Similar variants

CEP76 p.Arg568Pro Likely pathogenic ★ same type
CEP76 p.Cys478Arg Likely pathogenic ★ same type
CEP76 p.Ile101Thr Likely pathogenic ★ ⚠ same type
CEP76 p.Leu166Pro Likely pathogenic ★ same type
CEP76 p.Lys374= Pathogenic ★ same type
CEP76 p.Pro103Ser Pathogenic ★ ⚠ same type
CEP76 p.Val24Asp 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-val324phe (accessed [today's date]).

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