Is ALG13 p.Ala1044Val (c.3131C>T) pathogenic?

ALG13 p.Ala1044Val (c.3131C>T) is classified Likely benign in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.0757); Ultra-rare (popmax 0.0232%, mid); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Ala1044Val (c.3131C>T)?

ALG13 p.Ala1044Val (c.3131C>T) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Ala1044Val (c.3131C>T) in the general population?

ALG13 p.Ala1044Val (c.3131C>T) is ultra-rare (popmax 0.0232%, mid) (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.Ala1044Val (c.3131C>T)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

ALG13 p.Ala1044Val

c.3131C>T · rs761786951 · VCV2887885

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0232%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.97	GERP -3.8
Regional constraint	o/e 1.05	unconstrained · MANE · 2,374 bp · p 0.62 · regional, not allelic
Overall
CADD	0.05	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 0.0232% Middle Eastern · 1/4,317 alleles

Filtering AF 0.000743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000498% 6/1,204,190 alleles · ultra-rare exomes 4/1,093,154 · genomes 2/111,036 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0232%	4,317
Admixed American	0.00448%	22,318
Remaining individualsnot grpmax-eligible	0.00211%	47,369
European (non-Finnish)	0.000224%	446,634

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.Ala1044Val
Coding: c.3131C>T
MANE Select: NM_001099922
dbSNP: rs761786951
Type: single nucleotide variant
Location: chrX:111757745 (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.Ala1044Thr Uncertain significance ★★ ⚠ same residue
ALG13 p.Ala1044= Benign/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

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-ala1044val (accessed [today's date]).

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