Is CEP78 p.Thr511Arg (c.1532C>G) pathogenic?

CEP78 p.Thr511Arg (c.1532C>G) is classified Conflicting classifications of pathogenicity in CEP78 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.2311); Ultra-rare (popmax 0.0591%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP78 p.Thr511Arg (c.1532C>G)?

CEP78 p.Thr511Arg (c.1532C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP78 p.Thr511Arg (c.1532C>G) in the general population?

CEP78 p.Thr511Arg (c.1532C>G) is ultra-rare (popmax 0.0591%, amr) (gnomAD).

What do computational predictors say about CEP78 p.Thr511Arg (c.1532C>G)?

AlphaMissense predicts likely benign (score 0.2311) — an in-silico prediction, not a clinical call.

CEP78 p.Thr511Arg

c.1532C>G · rs764851727 · VCV934945

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2311 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0591%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2311	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.03	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	25.5	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 0.0591% Admixed American · 35/59,194 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.00224% 36/1,608,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0591%	1,691
European (non-Finnish)	8.49e-05%	1,177,410

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.Thr511Arg
Coding: c.1532C>G
MANE Select: NM_001330691
dbSNP: rs764851727
Type: single nucleotide variant
Location: chr9:78264223 (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.Thr511= Likely benign ★★ 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
CEP78 p.Ala47Thr Uncertain significance ★★ ⚠ same condition
CEP78 p.Ala56Val 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-thr511arg (accessed [today's date]).

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