Is ALG8 p.Leu288= (c.862T>C) pathogenic?

ALG8 p.Leu288= (c.862T>C) is classified Benign in ALG8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Leu288= (c.862T>C)?

ALG8 p.Leu288= (c.862T>C) is associated with ALG8-congenital disorder of glycosylation (ClinVar).

How is ALG8-CDG inherited?

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

ALG8 p.Leu288=

Q: How common is ALG8 p.Leu288= (c.862T>C) in the general population?

ALG8 p.Leu288= (c.862T>C) is common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.862T>C · rs61995924 · VCV306219

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele

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 3	GERP -3, phastCons 1
Overall
CADD	7.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.9% African / African-American · 11,208/74,990 alleles

Filtering AF 14.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 0.841% 13,576/1,614,042 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.9%	7
Remaining individualsnot grpmax-eligible	1.16%	87
Admixed American	1.09%	91
Middle Eastern	1.04%	96
East Asian	0.468%	214
South Asian	0.424%	236
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,741
European (non-Finnish)	0.0264%	3,782
Finnishnot grpmax-eligible	0.00156%	64,028

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.Leu288=
Coding: c.862T>C
MANE Select: NM_024079
dbSNP: rs61995924
Type: single nucleotide variant
Location: chr11:78112686 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 288: 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 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-leu288 (accessed [today's date]).

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