Is ALG8 p.Arg268Ter (c.802C>T) pathogenic?

ALG8 p.Arg268Ter (c.802C>T) is classified Pathogenic/Likely pathogenic in ALG8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-06). Very rare (popmax 0.00223%, eas); Associated with ALG8-related disorder.

What condition is associated with ALG8 p.Arg268Ter (c.802C>T)?

ALG8 p.Arg268Ter (c.802C>T) is associated with ALG8-related disorder, ALG8-congenital disorder of glycosylation (ClinVar).

How common is ALG8 p.Arg268Ter (c.802C>T) in the general population?

ALG8 p.Arg268Ter (c.802C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ALG8 p.Arg268Ter

c.802C>T · rs772492143 · VCV1406714

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

ALG8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.4, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Overall 0.00031% 5/1,613,706 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
East Asiangrpmax	0.00223%	44,876
Admixed American	0.00167%	59,970
Remaining individualsnot grpmax-eligible	0.0016%	62,472
Finnishnot grpmax-eligible	0.00156%	63,982

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.Arg268Ter
Coding: c.802C>T
MANE Select: NM_024079
dbSNP: rs772492143
Type: single nucleotide variant
Location: chr11:78112746 (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-related disorder

Also linked: ALG8-congenital disorder of glycosylation

Similar variants

ALG8 p.Arg268Gln Benign/Likely benign ★★ ⚠ 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-arg268ter (accessed [today's date]).

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