Is ALG5 p.Gly12= (c.36C>T) pathogenic?

ALG5 p.Gly12= (c.36C>T) is classified Benign in ALG5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-16). Rare (popmax 0.565%, afr); Associated with ALG5-related disorder.

What condition is associated with ALG5 p.Gly12= (c.36C>T)?

ALG5 p.Gly12= (c.36C>T) is associated with ALG5-related disorder (ClinVar).

How common is ALG5 p.Gly12= (c.36C>T) in the general population?

ALG5 p.Gly12= (c.36C>T) is rare (popmax 0.565%, afr) (gnomAD).

ALG5 p.Gly12=

c.36C>T · rs146902400 · VCV3040439

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.565%, 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	GERP -0.64, phastCons 0.028
Overall
CADD	7.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.565% African / African-American · 406/71,896 alleles

Filtering AF 0.519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.501%

Overall 0.033% 521/1,580,564 alleles · rare exomes 289/1,428,246 · genomes 232/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.565%	177
Admixed American	0.038%	2,631
Remaining individualsnot grpmax-eligible	0.0278%	3,595
East Asian	0.0124%	8,035
European (non-Finnish)	0.00617%	16,199

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.Gly12=
Coding: c.36C>T
MANE Select: NM_013338
dbSNP: rs146902400
Type: single nucleotide variant
Location: chr13:36999265 (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.Arg212Cys Uncertain significance ★ ⚠ same condition
ALG5 p.Ala19Ser Uncertain significance ⚠ same condition
ALG5 p.Arg79Gln Uncertain significance ⚠ same condition
ALG5 p.Ala18= Benign same condition
ALG5 p.Ala2= Likely benign same condition
ALG5 p.Leu11Val Likely benign same condition
ALG5 p.Thr249= Likely benign same condition
ALG5 p.Trp60Arg 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-gly12 (accessed [today's date]).

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