Is ALG13 p.Pro431= (c.1293A>G) pathogenic?

ALG13 p.Pro431= (c.1293A>G) is classified Benign in ALG13 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 34.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with ALG13 p.Pro431= (c.1293A>G)?

ALG13 p.Pro431= (c.1293A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 36 (ClinVar).

ALG13 p.Pro431=

Q: How common is ALG13 p.Pro431= (c.1293A>G) in the general population?

ALG13 p.Pro431= (c.1293A>G) is common (popmax 34.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1293A>G · rs7063657 · VCV380439

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 34.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 3.3	GERP 5.3, phastCons 1
Overall
CADD	5.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 34.6% African / African-American · 19,494/56,371 alleles

Filtering AF 34.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 34%

Overall 2.22% 26,506/1,192,281 alleles · common exomes 15,201/1,080,661 · genomes 11,305/111,620 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	34.6%	3
Middle Eastern	4.95%	20
Remaining individualsnot grpmax-eligible	3.17%	32
Admixed American	2.98%	34
Ashkenazi Jewishnot grpmax-eligible	1.54%	65
European (non-Finnish)	0.399%	251
South Asian	0.223%	449
Finnishnot grpmax-eligible	0.0348%	2,873
East Asian	0.00598%	16,727

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.Pro431=
Coding: c.1293A>G
MANE Select: NM_001099922
dbSNP: rs7063657
Type: single nucleotide variant
Location: chrX:111720137 (GRCh38)
Structure: AlphaFold pLDDT 54.42

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-pro431 (accessed [today's date]).

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