Is ALG1 p.Val39fs (c.115del) pathogenic?

ALG1 p.Val39fs (c.115del) is classified Conflicting classifications of pathogenicity in ALG1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-03-18). Very rare (popmax 0.00135%, afr); Associated with ALG1-related disorder.

What condition is associated with ALG1 p.Val39fs (c.115del)?

ALG1 p.Val39fs (c.115del) is associated with ALG1-related disorder, ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Val39fs (c.115del) in the general population?

ALG1 p.Val39fs (c.115del) is very rare (popmax 0.00135%, afr) (gnomAD).

ALG1 p.Val39fs

c.115del · rs886042130 · VCV281338

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

ALG1-related disorder

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 1 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.2, phastCons 1
Overall
CADD	31.0	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 0.00135% African / African-American · 1/74,288 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000377% 6/1,589,538 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	74,288
European (non-Finnish)	0.000428%	233,654

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: ALG1
Protein: p.Val39fs
Coding: c.115del
MANE Select: NM_019109
dbSNP: rs886042130
Type: Deletion
Location: chr16:5071963 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-related disorder

Also linked: ALG1-congenital disorder of glycosylation

Similar variants

ALG1 p.Ser330fs Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.741-13del Benign/Likely benign ★★ same condition
ALG1 c.287-12_289del Likely pathogenic ★ same condition
ALG1 p.Ala31fs Pathogenic ★ same condition
ALG1 p.Arg247fs Pathogenic ★ same condition
ALG1 p.Arg30fs Pathogenic ★ same condition
ALG1 p.Asp155fs Pathogenic ★ same condition
ALG1 p.Asp264fs 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/alg1-p-val39fs (accessed [today's date]).

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