Is ALG9 p.Gln526Glu (c.1576C>G) pathogenic?

ALG9 p.Gln526Glu (c.1576C>G) is classified Uncertain significance in ALG9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-17). AlphaMissense: likely benign (0.0957); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALG9 p.Gln526Glu (c.1576C>G)?

ALG9 p.Gln526Glu (c.1576C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALG9 p.Gln526Glu (c.1576C>G) in the general population?

ALG9 p.Gln526Glu (c.1576C>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ALG9 p.Gln526Glu (c.1576C>G)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

ALG9 p.Gln526Glu

c.1576C>G · rs926023630 · VCV3111430

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q519E vs ClinVar Q526E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,902 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00197% 3/152,146 alleles · very rare

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: ALG9
Protein: p.Gln526Glu
Coding: c.1576C>G
MANE Select: NM_024740
dbSNP: rs926023630
Type: single nucleotide variant
Location: chr11:111836191 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB

Full ALG9 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

Similar variants

ALG9 p.Arg607Gln Uncertain significance ★★ ⚠ same condition
ALG9 p.Ile130Val Uncertain significance ★★ ⚠ same condition
ALG9 p.Ser17Thr Uncertain significance ★★ ⚠ same condition
ALG9 p.Ala421Pro Uncertain significance ★ ⚠ same condition
ALG9 p.Arg42Trp Uncertain significance ★ ⚠ same condition
ALG9 p.Arg517Trp Uncertain significance ★ ⚠ same condition
ALG9 p.Arg584Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
ALG9 p.Gly37Asp Uncertain significance ★ ⚠ 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/alg9-p-gln526glu (accessed [today's date]).

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