Is ALG13 p.Met757Val (c.2269A>G) pathogenic?

ALG13 p.Met757Val (c.2269A>G) is classified Benign in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-20). AlphaMissense: likely benign (0.0596); Ultra-rare (popmax 0.0699%, amr); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Met757Val (c.2269A>G)?

ALG13 p.Met757Val (c.2269A>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Met757Val (c.2269A>G) in the general population?

ALG13 p.Met757Val (c.2269A>G) is ultra-rare (popmax 0.0699%, 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.Met757Val (c.2269A>G)?

AlphaMissense predicts likely benign (score 0.0596) — an in-silico prediction, not a clinical call.

ALG13 p.Met757Val

c.2269A>G · rs1451116623 · VCV764388

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0596 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0699%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.0596	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.22	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 1	GERP 1.6, phastCons 0.03
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	2.439	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 0.0699% Admixed American · 32/45,754 alleles

Filtering AF 0.0509% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.00322% 39/1,209,667 alleles · ultra-rare exomes 18/1,097,620 · genomes 21/112,047 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0699%	1,430
South Asian	0.00704%	14,195
European (non-Finnish)	0.000335%	298,308

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.Met757Val
Coding: c.2269A>G
MANE Select: NM_001099922
dbSNP: rs1451116623
Type: single nucleotide variant
Location: chrX:111728206 (GRCh38)
Structure: AlphaFold pLDDT 54.42

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.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-met757val (accessed [today's date]).

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