Is ALG3 p.Leu5Val (c.13C>G) pathogenic?

ALG3 p.Leu5Val (c.13C>G) is classified Uncertain significance in ALG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-29). AlphaMissense: likely benign (0.069); Ultra-rare (popmax 0.0141%, nfe); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Leu5Val (c.13C>G)?

ALG3 p.Leu5Val (c.13C>G) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Leu5Val (c.13C>G) in the general population?

ALG3 p.Leu5Val (c.13C>G) is ultra-rare (popmax 0.0141%, nfe) (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.Leu5Val (c.13C>G)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

ALG3 p.Leu5Val

c.13C>G · rs369888932 · VCV499704

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -2.3
Regional constraint	o/e 1.09	unconstrained · MANE · 3,742 bp · p 0.14 · regional, not allelic
Overall
CADD	7.606	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 0.0141% European (non-Finnish) · 165/1,166,558 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.0114% 180/1,583,534 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0141%	7,070
Remaining individualsnot grpmax-eligible	0.013%	7,663
African / African-American	0.0094%	10,635

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.Leu5Val
Coding: c.13C>G
MANE Select: NM_005787
dbSNP: rs369888932
Type: single nucleotide variant
Location: chr3:184248928 (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.Leu5Pro Uncertain significance ★ ⚠ same residue
ALG3 p.Gln5= Likely benign 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-leu5val (accessed [today's date]).

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