Is ALG6 p.Val169fs (c.506_507del) pathogenic?

ALG6 p.Val169fs (c.506507del) is classified Pathogenic/Likely pathogenic in ALG6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-25). Very rare (popmax 0.00153%, nfe); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Val169fs (c.506_507del)?

ALG6 p.Val169fs (c.506_507del) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Val169fs (c.506_507del) in the general population?

ALG6 p.Val169fs (c.506_507del) is very rare (popmax 0.00153%, nfe) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.Val169fs

c.506_507del · rs1274913587 · VCV1407854

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00153%, 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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 2.1, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,179,794 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00118% 19/1,613,500 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00153%	65,544
African / African-American	0.00134%	74,866

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.Val169fs
Coding: c.506_507del
MANE Select: NM_013339
dbSNP: rs1274913587
Type: Microsatellite
Location: chr1:63411155 (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.Val169= Likely benign ★ same residue
ALG6 p.Ile299del Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Phe264fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Tyr85fs Pathogenic ★ same condition
ALG6 p.Arg262del Uncertain significance ★ same condition
ALG6 p.Glu415del Uncertain significance ★ same condition
ALG6 p.Val239del Uncertain significance ★ same condition
ALG6 c.681-4_681-3insGTTTTTTTGTTTGTTT Likely benign ★ 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-val169fs (accessed [today's date]).

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