Is ALG5 p.Ala19Ser (c.55G>T) pathogenic?

ALG5 p.Ala19Ser (c.55G>T) is classified Uncertain significance in ALG5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.1197); Very rare (popmax 8.57e-05%, nfe); Associated with ALG5-related disorder.

What condition is associated with ALG5 p.Ala19Ser (c.55G>T)?

ALG5 p.Ala19Ser (c.55G>T) is associated with ALG5-related disorder (ClinVar).

How common is ALG5 p.Ala19Ser (c.55G>T) in the general population?

ALG5 p.Ala19Ser (c.55G>T) is very rare (popmax 8.57e-05%, nfe) (gnomAD).

What do computational predictors say about ALG5 p.Ala19Ser (c.55G>T)?

AlphaMissense predicts likely benign (score 0.1197) — an in-silico prediction, not a clinical call.

ALG5 p.Ala19Ser

c.55G>T · VCV3345153

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1197 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.57e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG5-related disorder

Computational evidence

Protein change
AlphaMissense	0.1197	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	15.19	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.57e-05% European (non-Finnish) · 1/1,166,342 alleles

Overall 7e-05% 1/1,428,422 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: ALG5
Protein: p.Ala19Ser
Coding: c.55G>T
MANE Select: NM_013338
Type: single nucleotide variant
Location: chr13:36999246 (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.Arg79Gln Uncertain significance ⚠ same condition
ALG5 p.Ala18= Benign 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
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-ala19ser (accessed [today's date]).

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