Is CEP78 p.Leu165Val (c.493T>G) pathogenic?

CEP78 p.Leu165Val (c.493T>G) is classified Uncertain significance in CEP78 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.1294); Absent from gnomAD v4.1.

How common is CEP78 p.Leu165Val (c.493T>G) in the general population?

CEP78 p.Leu165Val (c.493T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP78 p.Leu165Val (c.493T>G)?

AlphaMissense predicts likely benign (score 0.1294) — an in-silico prediction, not a clinical call.

CEP78 p.Leu165Val

c.493T>G · rs2489817546 · VCV2125110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1294 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1294	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.1	GERP 0.47, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	21.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP78
Protein: p.Leu165Val
Coding: c.493T>G
MANE Select: NM_001330691
dbSNP: rs2489817546
Type: single nucleotide variant
Location: chr9:78240358 (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-leu165val (accessed [today's date]).

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