Is ALG12 p.Asn334fs (c.1001del) pathogenic?

ALG12 p.Asn334fs (c.1001del) is classified Pathogenic/Likely pathogenic in ALG12 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-08-30). Ultra-rare (popmax 0.0217%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG12 p.Asn334fs (c.1001del)?

ALG12 p.Asn334fs (c.1001del) is associated with Inborn genetic diseases, ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Asn334fs (c.1001del) in the general population?

ALG12 p.Asn334fs (c.1001del) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

ALG12 p.Asn334fs

c.1001del · rs759244819 · VCV242854

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Conditions

Inborn genetic diseases

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 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.76	GERP -3
Overall
CADD	25.0	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 0.0217% Admixed American · 13/60,002 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00204% 33/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,616
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00267%	37,454
European (non-Finnish)	0.00119%	84,288

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: ALG12
Protein: p.Asn334fs
Coding: c.1001del
MANE Select: NM_024105
dbSNP: rs759244819
Type: Deletion
Location: chr22:49904498 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26

Full ALG12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG12-congenital disorder of glycosylation

Similar variants

ALG12 p.Arg311fs Pathogenic ★★ same condition
ALG12 p.Gln40fs Pathogenic ★★ same condition
ALG12 p.Leu12fs Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Lys416fs Likely pathogenic ★★ same condition
ALG12 p.Arg486fs Uncertain significance ★★ same condition
ALG12 c.439_469+19del Likely pathogenic ★ same condition
ALG12 c.664+1_664+9del Likely pathogenic ★ same condition
ALG12 p.Arg233fs 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/alg12-p-asn334fs (accessed [today's date]).

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