Is ALG1 p.Val457= (c.1371G>A) pathogenic?

ALG1 p.Val457= (c.1371G>A) is classified Likely benign in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). Very rare (popmax 0.00223%, eas); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Val457= (c.1371G>A)?

ALG1 p.Val457= (c.1371G>A) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Val457= (c.1371G>A) in the general population?

ALG1 p.Val457= (c.1371G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is ALG1-CDG inherited?

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

ALG1 p.Val457=

c.1371G>A · VCV3632040

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

ALG1-congenital disorder of glycosylation

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3	GERP -2, phastCons 1
Overall
CADD	4.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 6.26e-05% 1/1,596,396 alleles · very rare exomes 0/1,444,134 · genomes 1/152,262 · joint denominator

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: ALG1
Protein: p.Val457=
Coding: c.1371G>A
MANE Select: NM_019109
Type: single nucleotide variant
Location: chr16:5084857 (GRCh38)

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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/alg1-p-val457 (accessed [today's date]).

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