Is ALG11 p.Glu5fs (c.-4_13dup) pathogenic?

ALG11 p.Glu5fs (c.-413dup) is classified Uncertain significance in ALG11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-05). Ultra-rare (popmax 0.0944%, sas).

How common is ALG11 p.Glu5fs (c.-4_13dup) in the general population?

ALG11 p.Glu5fs (c.-4_13dup) is ultra-rare (popmax 0.0944%, sas) (gnomAD).

ALG11 p.Glu5fs

c.-4_13dup · rs746828347 · VCV1313498

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0944%, sas)

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 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.16	GERP -0.27, phastCons 0.1
Overall
CADD	8.869	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 0.0944% South Asian · 86/91,070 alleles

Filtering AF 0.0782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0723%

Overall 0.0057% 92/1,613,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0944%	1,059
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)	0.000169%	590,012

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: ALG11
Protein: p.Glu5fs
Coding: c.-4_13dup
MANE Select: NM_001004127
dbSNP: rs746828347
Type: Duplication
Location: chr13:52012409 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.40

Full ALG11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG11 p.Glu5Gly Uncertain significance ★★ ⚠ same residue
ALG11 p.Glu5Ter Likely pathogenic ★ same residue
ATP7B c.-123_-119dupCGCCG Benign/Likely benign ★★ same type
ALG11 p.Gly436fs Uncertain significance ★ same type
ALG11 c.1208-213dup Likely benign ★ same type
ALG11 c.276-194dup Benign ★ same type

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/alg11-p-glu5fs (accessed [today's date]).

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