Is ALG6 p.Leu307= (c.921G>A) pathogenic?

ALG6 p.Leu307= (c.921G>A) is classified Likely benign in ALG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Very rare (popmax 0.00661%, sas); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Leu307= (c.921G>A)?

ALG6 p.Leu307= (c.921G>A) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Leu307= (c.921G>A) in the general population?

ALG6 p.Leu307= (c.921G>A) is very rare (popmax 0.00661%, sas) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.Leu307=

c.921G>A · rs572008178 · VCV1115610

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00661%, sas)

Conditions

ALG6-congenital disorder of glycosylation 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Pangolin	Δ0.21	loss · gain 0.19 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 8.5	GERP 0.93, phastCons 1
Overall
CADD	15.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00661% South Asian · 6/90,830 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.000435% 7/1,610,118 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00661%	15,138
Remaining individualsnot grpmax-eligible	0.0016%	62,318

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.Leu307=
Coding: c.921G>A
MANE Select: NM_013339
dbSNP: rs572008178
Type: single nucleotide variant
Location: chr1:63415891 (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.Leu307Ter Pathogenic/Likely pathogenic ★★ same residue
ALG6 c.1128-1G>A Likely pathogenic ★★ same condition
ALG6 c.1128-2A>C Likely pathogenic ★★ same condition
ALG6 c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.257+5G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.429+1G>T Likely pathogenic ★★ same condition
ALG6 c.495-2A>G Likely pathogenic ★★ same condition
ALG6 c.495-2A>T 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-leu307 (accessed [today's date]).

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