Is ALG8 p.Thr64= (c.192G>A) pathogenic?

ALG8 p.Thr64= (c.192G>A) is classified Likely benign in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). Very rare (popmax 0.00669%, eas); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Thr64= (c.192G>A)?

ALG8 p.Thr64= (c.192G>A) is associated with ALG8-congenital disorder of glycosylation (ClinVar).

How common is ALG8 p.Thr64= (c.192G>A) in the general population?

ALG8 p.Thr64= (c.192G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

How is ALG8-CDG inherited?

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

ALG8 p.Thr64=

c.192G>A · rs368390661 · VCV2850349

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

ALG8-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	phastCons 1
Overall
CADD	8.662	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,870 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00112% 18/1,614,134 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
Admixed American	0.00333%	30,003
South Asian	0.0022%	45,541
European (non-Finnish)	0.000932%	107,275

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.Thr64=
Coding: c.192G>A
MANE Select: NM_024079
dbSNP: rs368390661
Type: single nucleotide variant
Location: chr11:78124197 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07

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.Thr64Met Uncertain significance ★★ ⚠ 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
ALG8 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg268Ter 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-thr64 (accessed [today's date]).

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