Is ALG13 p.Leu130Pro (c.389T>C) pathogenic?

ALG13 p.Leu130Pro (c.389T>C) is classified Likely benign in ALG13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-03). AlphaMissense: likely benign (0.05); Very rare (popmax 0.00291%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG13 p.Leu130Pro (c.389T>C)?

ALG13 p.Leu130Pro (c.389T>C) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Leu130Pro (c.389T>C) in the general population?

ALG13 p.Leu130Pro (c.389T>C) is very rare (popmax 0.00291%, nfe) (gnomAD).

What do computational predictors say about ALG13 p.Leu130Pro (c.389T>C)?

AlphaMissense predicts likely benign (score 0.05) — an in-silico prediction, not a clinical call.

ALG13 p.Leu130Pro

c.389T>C · rs1220905347 · VCV942999

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.05 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00291%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.05	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -5.53	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -6.4
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.23 · regional, not allelic
Overall
CADD	0.53	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 0.00291% European (non-Finnish) · 26/892,942 alleles

Filtering AF 0.00202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00172%

Overall 0.00232% 28/1,205,390 alleles · very rare exomes 27/1,093,636 · genomes 1/111,754 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00291%	34,344
Admixed American	0.0022%	45,403
Remaining individualsnot grpmax-eligible	0.00211%	47,413

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: ALG13
Protein: p.Leu130Pro
Coding: c.389T>C
MANE Select: NM_001099922
dbSNP: rs1220905347
Type: single nucleotide variant
Location: chrX:111708032 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 130: the 'deubiquitinase activity' region

Full ALG13 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

Also linked: developmental and epileptic encephalopathy, 36

Similar variants

ALG13 p.Leu130Val Uncertain significance ★ ⚠ same residue
ALG13 p.Asn107Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG13 c.2458-1G>A Uncertain significance ★★ same condition
ALG13 c.2695+4G>A Uncertain significance ★★ same condition
ALG13 c.2932+6T>C Uncertain significance ★★ same condition
ALG13 c.834+3A>G Uncertain significance ★★ same condition
ALG13 c.932+2T>C Uncertain significance ★★ same condition
ALG13 p.Ala1044Thr 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/alg13-p-leu130pro (accessed [today's date]).

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