Is ALG8 p.Val21= (c.63G>T) pathogenic?

ALG8 p.Val21= (c.63G>T) is classified Likely benign in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). Very rare (popmax 0.00355%, nfe); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Val21= (c.63G>T)?

ALG8 p.Val21= (c.63G>T) is associated with ALG8-congenital disorder of glycosylation (ClinVar).

How common is ALG8 p.Val21= (c.63G>T) in the general population?

ALG8 p.Val21= (c.63G>T) is very rare (popmax 0.00355%, nfe) (gnomAD).

How is ALG8-CDG inherited?

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

ALG8 p.Val21=

c.63G>T · VCV4698556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00355%, nfe)

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	<0.2	all four deltas below 0.2 · C>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP 1.5, phastCons 1
Overall
CADD	16.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00355% European (non-Finnish) · 41/1,153,346 alleles

Filtering AF 0.00264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00238%

Overall 0.00269% 42/1,563,254 alleles · very rare exomes 41/1,411,032 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00355%	28,130
Admixed American	0.0019%	52,542

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.Val21=
Coding: c.63G>T
MANE Select: NM_024079
Type: single nucleotide variant
Location: chr11:78139526 (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 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
ALG8 p.Arg364Ter 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-val21 (accessed [today's date]).

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