Is ALG1 p.Ala417Val (c.1250C>T) pathogenic?

ALG1 p.Ala417Val (c.1250C>T) is classified Uncertain significance in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-24). AlphaMissense: likely benign (0.1687); Absent from gnomAD v4.1; Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Ala417Val (c.1250C>T)?

ALG1 p.Ala417Val (c.1250C>T) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Ala417Val (c.1250C>T) in the general population?

ALG1 p.Ala417Val (c.1250C>T) is absent from gnomAD v4.1 (gnomAD).

How is ALG1-CDG inherited?

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

What do computational predictors say about ALG1 p.Ala417Val (c.1250C>T)?

AlphaMissense predicts likely benign (score 0.1687) — an in-silico prediction, not a clinical call.

ALG1 p.Ala417Val

c.1250C>T · VCV3580794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1687 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,838)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1687	likely benign
REVEL	0.696	pathogenic-leaning
SaProt	LLR -11.32	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.4, phastCons 0.99
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	26.2	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

No allele count reported in gnomAD v4.1 (AN 1,597,838). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALG1
Protein: p.Ala417Val
Coding: c.1250C>T
MANE Select: NM_019109
Type: single nucleotide variant
Location: chr16:5083744 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

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

Similar variants

ALG1 p.Ala417Gly Uncertain significance ★ ⚠ same residue
ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.1187+2T>C Pathogenic ★★ same condition
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.209-2A>G Likely pathogenic ★★ same condition
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.630-2A>G Likely pathogenic ★★ same condition
ALG1 c.863-2A>G Likely pathogenic ★★ 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/alg1-p-ala417val (accessed [today's date]).

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