Is ALG3 p.Arg171Gln (c.512G>A) pathogenic?

ALG3 p.Arg171Gln (c.512G>A) is classified Pathogenic/Likely pathogenic in ALG3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-22). AlphaMissense: likely pathogenic (0.8406); Ultra-rare (popmax 0.0102%, nfe); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Arg171Gln (c.512G>A)?

ALG3 p.Arg171Gln (c.512G>A) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Arg171Gln (c.512G>A) in the general population?

ALG3 p.Arg171Gln (c.512G>A) is ultra-rare (popmax 0.0102%, 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.Arg171Gln (c.512G>A)?

AlphaMissense predicts likely pathogenic (score 0.8406) — an in-silico prediction, not a clinical call.

ALG3 p.Arg171Gln

c.512G>A · rs119103236 · VCV2129

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.8406 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.8406	likely pathogenic ✓ concordant with ClinVar
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -13.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.33	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,742 bp · p 0.14 · regional, not allelic
Overall
CADD	35.0	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 0.0102% European (non-Finnish) · 120/1,179,746 alleles

Filtering AF 0.00867% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00812% 131/1,613,426 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0102%	9,831
African / African-American	0.00534%	18,720
Remaining individualsnot grpmax-eligible	0.0048%	20,819
East Asian	0.00223%	44,884
South Asian	0.0022%	45,506
Finnishnot grpmax-eligible	0.00156%	63,946

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.Arg171Gln
Coding: c.512G>A
MANE Select: NM_005787
dbSNP: rs119103236
Type: single nucleotide variant
Location: chr3:184245291 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05
Residue 171: a UniProt-annotated variant site (in cdg1d)

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.Arg171Trp Likely pathogenic ★ same residue
ALG3 c.444+1G>T 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
ALG3 p.Gly55= Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Ile69Thr 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-arg171gln (accessed [today's date]).

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