Is ALG3 p.Asn83Ser (c.248A>G) pathogenic?

ALG3 p.Asn83Ser (c.248A>G) is classified Uncertain significance in ALG3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.1127); Rare (popmax 0.105%, sas); Associated with Inborn genetic diseases.

What condition is associated with ALG3 p.Asn83Ser (c.248A>G)?

ALG3 p.Asn83Ser (c.248A>G) is associated with Inborn genetic diseases, ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Asn83Ser (c.248A>G) in the general population?

ALG3 p.Asn83Ser (c.248A>G) is rare (popmax 0.105%, sas) (gnomAD).

What do computational predictors say about ALG3 p.Asn83Ser (c.248A>G)?

AlphaMissense predicts likely benign (score 0.1127) — an in-silico prediction, not a clinical call.

ALG3 p.Asn83Ser

c.248A>G · rs199565095 · VCV1004509

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1127 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1127	likely benign
REVEL	0.61	indeterminate
SaProt	LLR -11.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.54, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,742 bp · p 0.14 · regional, not allelic
Overall
CADD	24.6	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 0.105% South Asian · 96/91,058 alleles

Filtering AF 0.0884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.082%

Overall 0.0192% 310/1,613,832 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.105%	949
Middle Eastern	0.0822%	1,217
European (non-Finnish)	0.0167%	5,989
Remaining individualsnot grpmax-eligible	0.008%	12,493
African / African-American	0.00534%	18,731
East Asian	0.00445%	22,447
Finnishnot grpmax-eligible	0.00156%	64,020

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.Asn83Ser
Coding: c.248A>G
MANE Select: NM_005787
dbSNP: rs199565095
Type: single nucleotide variant
Location: chr3:184245761 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG3-congenital disorder of glycosylation

Similar variants

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
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-asn83ser (accessed [today's date]).

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