Is ALG13 p.Val4Met (c.10G>A) pathogenic?

ALG13 p.Val4Met (c.10G>A) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). AlphaMissense: ambiguous (0.3945); Very rare (popmax 0.00174%, afr); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Val4Met (c.10G>A)?

ALG13 p.Val4Met (c.10G>A) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Val4Met (c.10G>A) in the general population?

ALG13 p.Val4Met (c.10G>A) is very rare (popmax 0.00174%, afr) (gnomAD).

How is ALG13-CDG inherited?

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

What do computational predictors say about ALG13 p.Val4Met (c.10G>A)?

AlphaMissense predicts ambiguous (score 0.3945) — an in-silico prediction, not a clinical call.

ALG13 p.Val4Met

c.10G>A · rs1245567722 · VCV1041615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3945 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.3945	ambiguous
REVEL	0.481	indeterminate
SaProt	LLR -11.94	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -2.1, phastCons 0.95
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.23 · regional, not allelic
Overall
CADD	19.49	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 0.00174% African / African-American · 1/57,540 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000496% 6/1,210,761 alleles · very rare exomes 5/1,097,911 · genomes 1/112,850 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00174%	57,540
European (non-Finnish)	0.000559%	179,032

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.Val4Met
Coding: c.10G>A
MANE Select: NM_001099922
dbSNP: rs1245567722
Type: single nucleotide variant
Location: chrX:111681228 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 4: the 'glycosyltransferase activity' region

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.Val4= Likely benign ★ 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-val4met (accessed [today's date]).

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