Is ALG5 p.Ala18= (c.54A>C) pathogenic?

ALG5 p.Ala18= (c.54A>C) is classified Benign in ALG5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-13). Rare (popmax 0.63%, afr); Associated with ALG5-related disorder.

What condition is associated with ALG5 p.Ala18= (c.54A>C)?

ALG5 p.Ala18= (c.54A>C) is associated with ALG5-related disorder (ClinVar).

How common is ALG5 p.Ala18= (c.54A>C) in the general population?

ALG5 p.Ala18= (c.54A>C) is rare (popmax 0.63%, afr) (gnomAD).

ALG5 p.Ala18=

c.54A>C · rs376568505 · VCV3051151

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.63%, afr)

Conditions

ALG5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -4
Overall
CADD	5.999	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.63% African / African-American · 453/71,934 alleles

Filtering AF 0.582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.563%

Overall 0.0316% 500/1,580,576 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.63%	159
Middle Eastern	0.0503%	1,987
Remaining individualsnot grpmax-eligible	0.0442%	2,264
Admixed American	0.0217%	4,603
South Asian	0.00343%	29,193
European (non-Finnish)	0.000171%	583,141

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: ALG5
Protein: p.Ala18=
Coding: c.54A>C
MANE Select: NM_013338
dbSNP: rs376568505
Type: single nucleotide variant
Location: chr13:36999247 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29

Full ALG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG5-related disorder

Similar variants

ALG5 p.Ala18Val Uncertain significance ★ ⚠ same residue
ALG5 p.Arg212Cys Uncertain significance ★ ⚠ same condition
ALG5 p.Ala19Ser Uncertain significance ⚠ same condition
ALG5 p.Arg79Gln Uncertain significance ⚠ same condition
ALG5 p.Ala2= Likely benign same condition
ALG5 p.Gly12= Benign same condition
ALG5 p.Leu11Val Likely benign same condition
ALG5 p.Thr249= 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/alg5-p-ala18 (accessed [today's date]).

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