Is ALG13 p.His641Arg (c.1922A>G) pathogenic?

ALG13 p.His641Arg (c.1922A>G) is classified Likely benign in ALG13 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-13). AlphaMissense: likely benign (0.1409); Ultra-rare (popmax 0.0481%, amr); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.His641Arg (c.1922A>G)?

ALG13 p.His641Arg (c.1922A>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.His641Arg (c.1922A>G) in the general population?

ALG13 p.His641Arg (c.1922A>G) is ultra-rare (popmax 0.0481%, amr) (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.His641Arg (c.1922A>G)?

AlphaMissense predicts likely benign (score 0.1409) — an in-silico prediction, not a clinical call.

ALG13 p.His641Arg

c.1922A>G · rs766772102 · VCV383125

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.1409	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP 5.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	17.76	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 0.0481% Admixed American · 22/45,731 alleles

Filtering AF 0.0326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.00198% 24/1,209,507 alleles · ultra-rare exomes 23/1,097,871 · genomes 1/111,636 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0481%	2,079
Remaining individualsnot grpmax-eligible	0.0042%	23,789

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.His641Arg
Coding: c.1922A>G
MANE Select: NM_001099922
dbSNP: rs766772102
Type: single nucleotide variant
Location: chrX:111727001 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 641: 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.His641Asp Conflicting classifications of pathogenicity ★ ⚠ 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
ALG13 p.Ala1044Thr 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-his641arg (accessed [today's date]).

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