Is CEP78 p.Ser366Arg (c.1098T>G) pathogenic?

CEP78 p.Ser366Arg (c.1098T>G) is classified Uncertain significance in CEP78 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-14). AlphaMissense: likely benign (0.2234); Very rare (popmax 0.000935%, nfe).

How common is CEP78 p.Ser366Arg (c.1098T>G) in the general population?

CEP78 p.Ser366Arg (c.1098T>G) is very rare (popmax 0.000935%, nfe) (gnomAD).

What do computational predictors say about CEP78 p.Ser366Arg (c.1098T>G)?

AlphaMissense predicts likely benign (score 0.2234) — an in-silico prediction, not a clinical call.

CEP78 p.Ser366Arg

c.1098T>G · rs757804379 · VCV2069288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000935%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2234	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.27	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 -0.81	GERP -2.4
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	10.6	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000935% European (non-Finnish) · 11/1,176,154 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000684% 11/1,608,298 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.Ser366Arg
Coding: c.1098T>G
MANE Select: NM_001330691
dbSNP: rs757804379
Type: single nucleotide variant
Location: chr9:78251936 (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 p.Ser366Thr Uncertain significance ★★ ⚠ same residue
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

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-ser366arg (accessed [today's date]).

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