Is ALG13 p.Met600Val (c.1798A>G) pathogenic?

ALG13 p.Met600Val (c.1798A>G) is classified Likely benign in ALG13 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0949); Ultra-rare (popmax 0.0326%, eas); Associated with Inborn genetic diseases.

What condition is associated with ALG13 p.Met600Val (c.1798A>G)?

ALG13 p.Met600Val (c.1798A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Met600Val (c.1798A>G) in the general population?

ALG13 p.Met600Val (c.1798A>G) is ultra-rare (popmax 0.0326%, eas) (gnomAD).

What do computational predictors say about ALG13 p.Met600Val (c.1798A>G)?

AlphaMissense predicts likely benign (score 0.0949) — an in-silico prediction, not a clinical call.

ALG13 p.Met600Val

c.1798A>G · rs189931917 · VCV430290

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0949 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0326%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0949	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -5.99	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 4	GERP 4.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	14.49	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 0.0326% East Asian · 11/33,732 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0141%

Overall 0.00736% 89/1,209,304 alleles · ultra-rare exomes 84/1,097,870 · genomes 5/111,434 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0326%	3,067
Remaining individualsnot grpmax-eligible	0.0315%	3,173
European (non-Finnish)	0.00693%	14,434
African / African-American	0.00175%	57,032

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.Met600Val
Coding: c.1798A>G
MANE Select: NM_001099922
dbSNP: rs189931917
Type: single nucleotide variant
Location: chrX:111726877 (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.Met600Thr 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
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-met600val (accessed [today's date]).

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