Is ALG3 p.Ala17Val (c.50C>T) pathogenic?

ALG3 p.Ala17Val (c.50C>T) is classified Uncertain significance in ALG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-09). AlphaMissense: likely benign (0.0897); Rare (popmax 0.117%, mid); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Ala17Val (c.50C>T)?

ALG3 p.Ala17Val (c.50C>T) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Ala17Val (c.50C>T) in the general population?

ALG3 p.Ala17Val (c.50C>T) is rare (popmax 0.117%, mid) (gnomAD).

How is ALG3-CDG inherited?

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

What do computational predictors say about ALG3 p.Ala17Val (c.50C>T)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

ALG3 p.Ala17Val

c.50C>T · rs776497657 · VCV2066390

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.117%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -7.79	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 2.9	GERP -2.4, phastCons 0.7
Regional constraint	o/e 1.09	unconstrained · MANE · 3,742 bp · p 0.14 · regional, not allelic
Overall
CADD	16.6	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 0.117% Middle Eastern · 7/5,988 alleles

Filtering AF 0.0548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0389%

Overall 0.00125% 20/1,602,678 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.117%	855
South Asian	0.00332%	30,103
Remaining individualsnot grpmax-eligible	0.00161%	61,952
European (non-Finnish)	0.000766%	130,587

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: ALG3
Protein: p.Ala17Val
Coding: c.50C>T
MANE Select: NM_005787
dbSNP: rs776497657
Type: single nucleotide variant
Location: chr3:184248891 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG3-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG3 p.Ala17= Conflicting classifications of pathogenicity ★ same residue
ALG3 p.Ala17Gly Uncertain significance ★ ⚠ same residue
ALG3 c.444+1G>T Likely pathogenic ★★ same condition
ALG3 p.Arg171Gln Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Arg266Cys Pathogenic ★★ same condition
ALG3 p.Arg354Cys Likely pathogenic ★★ same condition
ALG3 p.Arg354His Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Asn174Ser 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/alg3-p-ala17val (accessed [today's date]).

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