Is CEP78 p.Ser300Pro (c.898T>C) pathogenic?

CEP78 p.Ser300Pro (c.898T>C) is classified Likely benign in CEP78 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0926); Rare (popmax 0.25%, nfe).

How common is CEP78 p.Ser300Pro (c.898T>C) in the general population?

CEP78 p.Ser300Pro (c.898T>C) is rare (popmax 0.25%, nfe) (gnomAD).

What do computational predictors say about CEP78 p.Ser300Pro (c.898T>C)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

CEP78 p.Ser300Pro

c.898T>C · rs72743760 · VCV667088

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.25%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -8.32	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 3.3	GERP -2.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	21.5	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 0.25% European (non-Finnish) · 2,761/1,105,070 alleles

Filtering AF 0.242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.239%

Overall 0.201% 3,085/1,531,384 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.25%	400
Remaining individualsnot grpmax-eligible	0.201%	498
Admixed American	0.142%	704
Finnishnot grpmax-eligible	0.124%	809
Middle Eastern	0.0517%	1,936
African / African-American	0.0463%	2,160
Ashkenazi Jewishnot grpmax-eligible	0.0103%	9,683

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.Ser300Pro
Coding: c.898T>C
MANE Select: NM_001330691
dbSNP: rs72743760
Type: single nucleotide variant
Location: chr9:78248296 (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.Ser300Ala 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-ser300pro (accessed [today's date]).

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