Is ALG8 c.898+139C>T pathogenic?

ALG8 c.898+139C>T is classified Benign in ALG8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-14). Common (popmax 68.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 c.898+139C>T?

ALG8 c.898+139C>T 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 c.898+139C>T

Q: How common is ALG8 c.898+139C>T in the general population?

ALG8 c.898+139C>T is common (popmax 68.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs624350 · VCV1188963

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 68.6%, nfe) — 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
Splice region	donor +139	deep intronic (+139 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -0.56
Non-coding constraint	Z -2.63	1 kb window · o/e 1.21 · regional · uncalibrated
Overall
CADD	4.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.6% European (non-Finnish) · 633,533/923,652 alleles

Filtering AF 68.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 68.4%

Overall 65.8% 858,185/1,304,430 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	72.6%	1
Ashkenazi Jewishnot grpmax-eligible	71.1%	1
European (non-Finnish)grpmax	68.6%	1
Middle Eastern	66%	2
Remaining individualsnot grpmax-eligible	65.3%	2
South Asian	61.1%	2
Admixed American	54.7%	2
Amishnot grpmax-eligible	53%	2
African / African-American	53%	2
East Asian	37.5%	3

Finnish 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
Coding: c.898+139C>T
MANE Select: NM_024079
dbSNP: rs624350
Type: single nucleotide variant
Location: chr11:78112511 (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

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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-c-898-plus-139c-t (accessed [today's date]).

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