Is CEP78 p.Ser4Phe (c.11C>T) pathogenic?

CEP78 p.Ser4Phe (c.11C>T) is classified Uncertain significance in CEP78 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-08). AlphaMissense: likely pathogenic (0.7122); Very rare (popmax 0.00437%, nfe).

How common is CEP78 p.Ser4Phe (c.11C>T) in the general population?

CEP78 p.Ser4Phe (c.11C>T) is very rare (popmax 0.00437%, nfe) (gnomAD).

What do computational predictors say about CEP78 p.Ser4Phe (c.11C>T)?

AlphaMissense predicts likely pathogenic (score 0.7122) — an in-silico prediction, not a clinical call.

CEP78 p.Ser4Phe

c.11C>T · rs758699168 · VCV1394129

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00437%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7122	likely pathogenic
REVEL	0.108	moderately benign-leaning
SaProt	LLR -0.34	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.44, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · 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

Grpmax group 0.00437% European (non-Finnish) · 51/1,166,172 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00306%

Overall 0.00323% 51/1,578,492 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.Ser4Phe
Coding: c.11C>T
MANE Select: NM_001330691
dbSNP: rs758699168
Type: single nucleotide variant
Location: chr9:78236361 (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-ser4phe (accessed [today's date]).

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