Is CLYBL p.Glu103Asp (c.309A>C) pathogenic?

CLYBL p.Glu103Asp (c.309A>C) is classified Uncertain significance in CLYBL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely pathogenic (0.6904); Very rare (popmax 0.00801%, afr).

How common is CLYBL p.Glu103Asp (c.309A>C) in the general population?

CLYBL p.Glu103Asp (c.309A>C) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CLYBL p.Glu103Asp (c.309A>C)?

AlphaMissense predicts likely pathogenic (score 0.6904) — an in-silico prediction, not a clinical call.

CLYBL p.Glu103Asp

c.309A>C · VCV3834267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6904	likely pathogenic
REVEL	0.141	moderately benign-leaning
SaProt	LLR -10.02	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 285 kb · p 0.27 · regional, not allelic
Overall
CADD	19.09	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 0.00801% African / African-American · 6/74,932 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000372% 6/1,613,936 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: CLYBL
Protein: p.Glu103Asp
Coding: c.309A>C
MANE Select: NM_206808
Type: single nucleotide variant
Location: chr13:99858920 (GRCh38)
Gene constraint: LOEUF 1.186 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 3 PDB
Residue 103: a β-strand

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-glu103asp (accessed [today's date]).

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