Is CEP78 p.Arg95Pro (c.284G>C) pathogenic?

CEP78 p.Arg95Pro (c.284G>C) is classified Uncertain significance in CEP78 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: ambiguous (0.4231); Very rare (popmax 0.000171%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP78 p.Arg95Pro (c.284G>C)?

CEP78 p.Arg95Pro (c.284G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP78 p.Arg95Pro (c.284G>C) in the general population?

CEP78 p.Arg95Pro (c.284G>C) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about CEP78 p.Arg95Pro (c.284G>C)?

AlphaMissense predicts ambiguous (score 0.4231) — an in-silico prediction, not a clinical call.

CEP78 p.Arg95Pro

c.284G>C · rs371010271 · VCV3143050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4231	ambiguous
REVEL	0.369	indeterminate
SaProt	LLR -6.95	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.85, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.000171% European (non-Finnish) · 2/1,172,128 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00014% 2/1,429,546 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CEP78
Protein: p.Arg95Pro
Coding: c.284G>C
MANE Select: NM_001330691
dbSNP: rs371010271
Type: single nucleotide variant
Location: chr9:78240053 (GRCh38)
Gene constraint: LOEUF 1.531 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.28

Full CEP78 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP78 p.Arg95Cys Uncertain significance ★ ⚠ same residue
CEP78 p.Arg95Gly Uncertain significance ★ ⚠ same residue
CEP78 p.Arg95His Uncertain significance ★★ ⚠ same residue
CEP78 c.2107+37C>T Uncertain significance ★★ same condition
CEP78 p.Ala304Thr Uncertain significance ★★ ⚠ same condition
CEP78 p.Ala378Val Uncertain significance ★★ ⚠ same condition
CEP78 p.Ala380Ser Uncertain significance ★★ ⚠ same condition
CEP78 p.Ala380Thr 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/cep78-p-arg95pro (accessed [today's date]).

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