Is CEP78 p.Ser694Phe (c.2081C>T) pathogenic?

CEP78 p.Ser694Phe (c.2081C>T) is classified Uncertain significance in CEP78 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-08). AlphaMissense: likely benign (0.0873); Very rare (popmax 8.48e-05%, nfe).

How common is CEP78 p.Ser694Phe (c.2081C>T) in the general population?

CEP78 p.Ser694Phe (c.2081C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CEP78 p.Ser694Phe (c.2081C>T)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

CEP78 p.Ser694Phe

c.2081C>T · rs1236286966 · VCV1515339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -9.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP 1.9
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S678F vs ClinVar S694F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,020 alleles

Overall 6.85e-05% 1/1,459,842 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.Ser694Phe
Coding: c.2081C>T
MANE Select: NM_001330691
dbSNP: rs1236286966
Type: single nucleotide variant
Location: chr9:78266677 (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

Similar variants

CEP78 c.1205+2T>A Pathogenic/Likely pathogenic ★★ same type
CEP78 c.1206-2A>C Pathogenic ★★ same type
CEP78 c.1206-2A>G Pathogenic/Likely pathogenic ★★ same type
CEP78 c.1251+5G>A Pathogenic/Likely pathogenic ★★ same type
CEP78 c.254-1G>T Pathogenic/Likely pathogenic ★★ same type
CEP78 c.778+1G>A Likely pathogenic ★★ same type
CEP78 p.Arg483Ter Pathogenic/Likely pathogenic ★★ same type
CEP78 p.Cys158Phe Pathogenic/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/cep78-p-ser694phe (accessed [today's date]).

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