Is ALG13 p.Pro927= (c.2781A>C) pathogenic?

ALG13 p.Pro927= (c.2781A>C) is classified Likely benign in ALG13 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0181%, nfe); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Pro927= (c.2781A>C)?

ALG13 p.Pro927= (c.2781A>C) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Pro927= (c.2781A>C) in the general population?

ALG13 p.Pro927= (c.2781A>C) is ultra-rare (popmax 0.0181%, nfe) (gnomAD).

How is ALG13-CDG inherited?

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

ALG13 p.Pro927=

c.2781A>C · rs147870070 · VCV718111

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.53	GERP -3.6
Overall
CADD	0.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% European (non-Finnish) · 107/590,626 alleles

Filtering AF 0.0153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.0177% 139/787,433 alleles · ultra-rare exomes 132/720,946 · genomes 7/66,487 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0444%	2,254
Remaining individualsnot grpmax-eligible	0.028%	3,577
European (non-Finnish)grpmax	0.0181%	5,520
African / African-American	0.014%	7,126
South Asian	0.00827%	12,095
Ashkenazi Jewishnot grpmax-eligible	0.007%	14,293
Admixed American	0.00698%	14,333
East Asian	0.00448%	22,299

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro927=
Coding: c.2781A>C
MANE Select: NM_001099922
dbSNP: rs147870070
Type: single nucleotide variant
Location: chrX:111744753 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 927: the 'disordered' 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.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-pro927 (accessed [today's date]).

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