Is ALG13 p.Asn511Ser (c.1532A>G) pathogenic?

ALG13 p.Asn511Ser (c.1532A>G) is classified Uncertain significance in ALG13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-22). AlphaMissense: likely benign (0.1371); Very rare (popmax 0.00034%, nfe); Associated with ALG13-related disorder.

What condition is associated with ALG13 p.Asn511Ser (c.1532A>G)?

ALG13 p.Asn511Ser (c.1532A>G) is associated with ALG13-related disorder, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Asn511Ser (c.1532A>G) in the general population?

ALG13 p.Asn511Ser (c.1532A>G) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about ALG13 p.Asn511Ser (c.1532A>G)?

AlphaMissense predicts likely benign (score 0.1371) — an in-silico prediction, not a clinical call.

ALG13 p.Asn511Ser

c.1532A>G · rs2525861997 · VCV2637047

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1371 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ALG13-related disorder

Computational evidence

Protein change
AlphaMissense	0.1371	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -6.06	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 7	GERP 5.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	24.0	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 0.00034% European (non-Finnish) · 3/881,381 alleles

Filtering AF 9.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000253% 3/1,186,289 alleles · very rare exomes 3/1,072,483 · genomes 0/113,806 · joint denominator

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.Asn511Ser
Coding: c.1532A>G
MANE Select: NM_001099922
dbSNP: rs2525861997
Type: single nucleotide variant
Location: chrX:111723829 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 511: the tudor domain

Full ALG13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG13-related disorder

Also linked: developmental and epileptic encephalopathy, 36

Similar variants

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
ALG13 p.Ala173Val 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-asn511ser (accessed [today's date]).

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