Is ALG1 p.Gly268Arg (c.802G>A) pathogenic?

ALG1 p.Gly268Arg (c.802G>A) is classified Conflicting classifications of pathogenicity in ALG1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1185); Ultra-rare (popmax 0.0198%, mid); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Gly268Arg (c.802G>A)?

ALG1 p.Gly268Arg (c.802G>A) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Gly268Arg (c.802G>A) in the general population?

ALG1 p.Gly268Arg (c.802G>A) is ultra-rare (popmax 0.0198%, mid) (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.Gly268Arg (c.802G>A)?

AlphaMissense predicts likely benign (score 0.1185) — an in-silico prediction, not a clinical call.

ALG1 p.Gly268Arg

c.802G>A · rs148611855 · VCV1585998

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1185 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1185	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -10.83	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -2, phastCons 0.99
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	17.88	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 0.0198% Middle Eastern · 1/5,060 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.0116% 187/1,612,460 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0198%	5,060
Admixed American	0.0167%	6,000
European (non-Finnish)	0.0139%	7,194
Remaining individualsnot grpmax-eligible	0.0112%	8,906
African / African-American	0.00401%	24,962
Finnishnot grpmax-eligible	0.00156%	63,958
South Asian	0.0011%	91,010

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: ALG1
Protein: p.Gly268Arg
Coding: c.802G>A
MANE Select: NM_019109
dbSNP: rs148611855
Type: single nucleotide variant
Location: chr16:5078818 (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.Gly268Trp 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-gly268arg (accessed [today's date]).

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