Is ALG13 p.Val47Ile (c.139G>A) pathogenic?

ALG13 p.Val47Ile (c.139G>A) is classified Conflicting classifications of pathogenicity in ALG13 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0841); Ultra-rare (popmax 0.0179%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG13 p.Val47Ile (c.139G>A)?

ALG13 p.Val47Ile (c.139G>A) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Val47Ile (c.139G>A) in the general population?

ALG13 p.Val47Ile (c.139G>A) is ultra-rare (popmax 0.0179%, amr) (gnomAD).

What do computational predictors say about ALG13 p.Val47Ile (c.139G>A)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

ALG13 p.Val47Ile

c.139G>A · rs766512298 · VCV702857

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -7.30	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 6.3	GERP 0.34, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.23 · regional, not allelic
Overall
CADD	21.5	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 0.0179% Admixed American · 8/44,584 alleles

Filtering AF 0.00889% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00644%

Overall 0.000834% 10/1,199,753 alleles · ultra-rare exomes 10/1,086,217 · genomes 0/113,536 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0179%	5,573
Finnishnot grpmax-eligible	0.00429%	23,319

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.Val47Ile
Coding: c.139G>A
MANE Select: NM_001099922
dbSNP: rs766512298
Type: single nucleotide variant
Location: chrX:111682189 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 47: the 'glycosyltransferase activity' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-val47ile (accessed [today's date]).

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