Is ALG13 p.Ile911Val (c.2731A>G) pathogenic?

ALG13 p.Ile911Val (c.2731A>G) is classified Uncertain significance in ALG13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-01). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.00477%, amr); Associated with developmental and epileptic encephalopathy.

What condition is associated with ALG13 p.Ile911Val (c.2731A>G)?

ALG13 p.Ile911Val (c.2731A>G) is associated with developmental and epileptic encephalopathy, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Ile911Val (c.2731A>G) in the general population?

ALG13 p.Ile911Val (c.2731A>G) is very rare (popmax 0.00477%, amr) (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG13 p.Ile911Val (c.2731A>G)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

ALG13 p.Ile911Val

c.2731A>G · rs1392307065 · VCV2173691

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00477%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.21	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 0.46	GERP -7.8, phastCons 0.061
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	0.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00477% Admixed American · 2/41,926 alleles

Filtering AF 0.000791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000296%

Overall 0.00051% 6/1,177,558 alleles · very rare exomes 6/1,068,281 · genomes 0/109,277 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00477%	20,963
South Asian	0.00189%	52,918
European (non-Finnish)	0.000341%	293,681

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.Ile911Val
Coding: c.2731A>G
MANE Select: NM_001099922
dbSNP: rs1392307065
Type: single nucleotide variant
Location: chrX:111744703 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 911: the 'disordered' region

Full ALG13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 36

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

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-ile911val (accessed [today's date]).

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