Is ALG8 p.Arg268Gln (c.803G>A) pathogenic?

ALG8 p.Arg268Gln (c.803G>A) is classified Benign/Likely benign in ALG8 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.2283); Low-frequency (popmax 2.24%, nfe); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Arg268Gln (c.803G>A)?

ALG8 p.Arg268Gln (c.803G>A) is associated with ALG8-congenital disorder of glycosylation (ClinVar).

How common is ALG8 p.Arg268Gln (c.803G>A) in the general population?

ALG8 p.Arg268Gln (c.803G>A) is low-frequency (popmax 2.24%, nfe) (gnomAD).

How is ALG8-CDG inherited?

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

What do computational predictors say about ALG8 p.Arg268Gln (c.803G>A)?

AlphaMissense predicts likely benign (score 0.2283) — an in-silico prediction, not a clinical call.

ALG8 p.Arg268Gln

c.803G>A · rs61995925 · VCV96093

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.2283 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.24%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG8-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2283	likely benign
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -13.74	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	28.6	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 2.24% European (non-Finnish) · 26,432/1,179,792 alleles

Filtering AF 2.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.21%

Overall 1.89% 30,561/1,613,666 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.58%	28
European (non-Finnish)grpmax	2.24%	45
Remaining individualsnot grpmax-eligible	1.68%	60
Finnishnot grpmax-eligible	1.6%	63
Admixed American	0.774%	129
African / African-American	0.413%	242
South Asian	0.238%	419
Middle Eastern	0.099%	1,010
East Asian	0.00223%	44,864

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ALG8
Protein: p.Arg268Gln
Coding: c.803G>A
MANE Select: NM_024079
dbSNP: rs61995925
Type: single nucleotide variant
Location: chr11:78112745 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 268: a UniProt-annotated variant site (in pcld3)

Full ALG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG8-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG8-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same residue
ALG8 p.Arg268Leu Uncertain significance ★ ⚠ same residue
ALG8 p.Arg268fs Pathogenic/Likely pathogenic ★★ same residue
ALG8 c.368+2T>G Likely pathogenic ★★ same condition
ALG8 c.674-2A>G Likely pathogenic ★★ same condition
ALG8 c.777+1G>A Likely pathogenic ★★ same condition
ALG8 c.95+1G>A Likely pathogenic ★★ same condition
ALG8 p.Arg179Ter Pathogenic/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/alg8-p-arg268gln (accessed [today's date]).

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