Is ALG13 p.Gly422= (c.1266T>C) pathogenic?

ALG13 p.Gly422= (c.1266T>C) is classified Benign in ALG13 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.97%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG13 p.Gly422= (c.1266T>C)?

ALG13 p.Gly422= (c.1266T>C) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Gly422= (c.1266T>C) in the general population?

ALG13 p.Gly422= (c.1266T>C) is low-frequency (popmax 1.97%, nfe) (gnomAD).

ALG13 p.Gly422=

c.1266T>C · rs5985637 · VCV238289

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.97%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP 4.1, phastCons 1
Overall
CADD	7.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.97% European (non-Finnish) · 17,378/882,696 alleles

Filtering AF 1.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.93%

Overall 1.67% 19,838/1,188,699 alleles · low-frequency exomes 18,322/1,076,664 · genomes 1,516/112,035 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	20.1%	5
European (non-Finnish)grpmax	1.97%	51
Middle Eastern	1.81%	55
Admixed American	1.62%	62
Remaining individualsnot grpmax-eligible	1.61%	62
Ashkenazi Jewishnot grpmax-eligible	1.46%	68
Finnishnot grpmax-eligible	0.447%	224
South Asian	0.255%	393
African / African-American	0.226%	443
East Asian	0.00299%	33,460

Amish 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.Gly422=
Coding: c.1266T>C
MANE Select: NM_001099922
dbSNP: rs5985637
Type: single nucleotide variant
Location: chrX:111720110 (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.Gly422Val Uncertain significance ★★ ⚠ same residue
ALG13 p.Gly422Ala Uncertain significance ★ ⚠ same residue
ALG13 p.Gly422Ser Uncertain significance ★ ⚠ 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

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-gly422 (accessed [today's date]).

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