Is ALG6 p.His79del (c.235_237del) pathogenic?

ALG6 p.His79del (c.235237del) is classified Uncertain significance in ALG6 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-05). Very rare (popmax 0.00034%, nfe); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.His79del (c.235_237del)?

ALG6 p.His79del (c.235_237del) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.His79del (c.235_237del) in the general population?

ALG6 p.His79del (c.235_237del) is very rare (popmax 0.00034%, nfe) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.His79del

c.235_237del · rs1297610094 · VCV556815

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Conditions

ALG6-congenital disorder of glycosylation 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,177,530 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,458,918 alleles · very rare

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: ALG6
Protein: p.His79del
Coding: c.235_237del
MANE Select: NM_013339
dbSNP: rs1297610094
Type: Deletion
Location: chr1:63402319 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.08

Full ALG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG6-congenital disorder of glycosylation 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG6-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG6 p.His79Gln Uncertain significance ★ ⚠ same residue
ALG6 p.His79Leu Uncertain significance ★ ⚠ same residue
ALG6 c.82_82+8del Likely pathogenic ★★ same condition
ALG6 p.Asn283fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Gln417fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Leu416fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Met34fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Phe228fs 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/alg6-p-his79del (accessed [today's date]).

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