Is CLYBL p.Leu18Val (c.52C>G) pathogenic?

CLYBL p.Leu18Val (c.52C>G) is classified Uncertain significance in CLYBL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.081); Absent from gnomAD v4.1.

How common is CLYBL p.Leu18Val (c.52C>G) in the general population?

CLYBL p.Leu18Val (c.52C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLYBL p.Leu18Val (c.52C>G)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

CLYBL p.Leu18Val

c.52C>G · rs370813733 · VCV3146186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -5.88	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 1.7	GERP -0.51, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 285 kb · p 0.27 · regional, not allelic
Overall
CADD	17.43	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: CLYBL
Protein: p.Leu18Val
Coding: c.52C>G
MANE Select: NM_206808
dbSNP: rs370813733
Type: single nucleotide variant
Location: chr13:99606747 (GRCh38)
Gene constraint: LOEUF 1.186 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 3 PDB

Full CLYBL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLYBL p.Ala116Val Uncertain significance ★ ⚠ same type
CLYBL p.Ala13Asp Uncertain significance ★ ⚠ same type
CLYBL p.Ala13Val Uncertain significance ★ ⚠ same type
CLYBL p.Ala16Val Uncertain significance ★ ⚠ same type
CLYBL p.Ala17Ser Uncertain significance ★ ⚠ same type
CLYBL p.Ala17Thr Uncertain significance ★ ⚠ same type
CLYBL p.Ala17Val Uncertain significance ★ ⚠ same type
CLYBL p.Ala213Ser Uncertain significance ★ ⚠ 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/clybl-p-leu18val (accessed [today's date]).

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