Is CLYBL p.Ala13Val (c.38C>T) pathogenic?

CLYBL p.Ala13Val (c.38C>T) is classified Uncertain significance in CLYBL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.2517); Ultra-rare (popmax 0.0236%, nfe).

How common is CLYBL p.Ala13Val (c.38C>T) in the general population?

CLYBL p.Ala13Val (c.38C>T) is ultra-rare (popmax 0.0236%, nfe) (gnomAD).

What do computational predictors say about CLYBL p.Ala13Val (c.38C>T)?

AlphaMissense predicts likely benign (score 0.2517) — an in-silico prediction, not a clinical call.

CLYBL p.Ala13Val

c.38C>T · rs759290602 · VCV2592637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2517 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2517	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.053	GERP -0.8, phastCons 0.008
Regional constraint	o/e 1.05	unconstrained · MANE · 285 kb · p 0.27 · regional, not allelic
Overall
CADD	15.71	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

Grpmax group 0.0236% European (non-Finnish) · 266/1,125,106 alleles

Filtering AF 0.0213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0204%

Overall 0.0188% 280/1,487,530 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0236%	4,230
Remaining individualsnot grpmax-eligible	0.0122%	8,227
African / African-American	0.0103%	9,725

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.Ala13Val
Coding: c.38C>T
MANE Select: NM_206808
dbSNP: rs759290602
Type: single nucleotide variant
Location: chr13:99606733 (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.Ala13Asp Uncertain significance ★ ⚠ same residue
CLYBL p.Ala116Val 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
CLYBL p.Ala235Gly 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-ala13val (accessed [today's date]).

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