Is ALG11 p.Ala450Val (c.1349C>T) pathogenic?

ALG11 p.Ala450Val (c.1349C>T) is classified Likely benign in ALG11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0904); Rare (popmax 0.125%, sas); Associated with ALG11-congenital disorder of glycosylation.

What condition is associated with ALG11 p.Ala450Val (c.1349C>T)?

ALG11 p.Ala450Val (c.1349C>T) is associated with ALG11-congenital disorder of glycosylation (ClinVar).

How common is ALG11 p.Ala450Val (c.1349C>T) in the general population?

ALG11 p.Ala450Val (c.1349C>T) is rare (popmax 0.125%, sas) (gnomAD).

How is ALG11-CDG inherited?

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

What do computational predictors say about ALG11 p.Ala450Val (c.1349C>T)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

ALG11 p.Ala450Val

c.1349C>T · rs757069433 · VCV961247

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG11-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -7.69	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 2.2	GERP 1.7, phastCons 0.97
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	19.15	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 0.125% South Asian · 114/91,086 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0994%

Overall 0.00737% 119/1,614,062 alleles · rare exomes 114/1,461,892 · genomes 5/152,170 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.125%	799
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0048%	20,829

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: ALG11
Protein: p.Ala450Val
Coding: c.1349C>T
MANE Select: NM_001004127
dbSNP: rs757069433
Type: single nucleotide variant
Location: chr13:52028460 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.40

Full ALG11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG11-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG11-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG11 c.45-2A>T Likely pathogenic ★★ same condition
ALG11 p.Arg468Cys Likely pathogenic ★★ ⚠ same condition
ALG11 p.Arg468His Likely pathogenic ★★ same condition
ALG11 p.Met1Val Likely pathogenic ★★ same condition
ALG11 c.*540T>A Uncertain significance ★★ ⚠ same condition
ALG11 p.Arg136Cys Uncertain significance ★★ same condition
ALG11 p.Arg15Thr Uncertain significance ★★ ⚠ same condition
ALG11 p.Arg346His 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/alg11-p-ala450val (accessed [today's date]).

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