Is ALG13 p.Val1004= (c.3012G>A) pathogenic?

ALG13 p.Val1004= (c.3012G>A) is classified Likely benign in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). Very rare (popmax 0.00595%, eas); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Val1004= (c.3012G>A)?

ALG13 p.Val1004= (c.3012G>A) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Val1004= (c.3012G>A) in the general population?

ALG13 p.Val1004= (c.3012G>A) is very rare (popmax 0.00595%, eas) (gnomAD).

How is ALG13-CDG inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALG13 p.Val1004=

c.3012G>A · rs1569523963 · VCV3019056

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00595%, eas)

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.5	GERP 1.9, phastCons 1
Overall
CADD	5.835	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00595% East Asian · 2/33,610 alleles

Filtering AF 0.000986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000369%

Overall 0.000166% 2/1,205,849 alleles · very rare exomes 1/1,096,227 · genomes 1/109,622 · 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.Val1004=
Coding: c.3012G>A
MANE Select: NM_001099922
dbSNP: rs1569523963
Type: single nucleotide variant
Location: chrX:111757626 (GRCh38)
Structure: AlphaFold pLDDT 54.42

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

Disease context

developmental and epileptic encephalopathy, 36 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG13-CDG (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

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-val1004 (accessed [today's date]).

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