Is ALG5 p.Arg79Gln (c.236G>A) pathogenic?

ALG5 p.Arg79Gln (c.236G>A) is classified Uncertain significance in ALG5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-28). AlphaMissense: likely pathogenic (0.7801); Very rare (popmax 0.000424%, nfe); Associated with ALG5-related disorder.

What condition is associated with ALG5 p.Arg79Gln (c.236G>A)?

ALG5 p.Arg79Gln (c.236G>A) is associated with ALG5-related disorder (ClinVar).

How common is ALG5 p.Arg79Gln (c.236G>A) in the general population?

ALG5 p.Arg79Gln (c.236G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ALG5 p.Arg79Gln (c.236G>A)?

AlphaMissense predicts likely pathogenic (score 0.7801) — an in-silico prediction, not a clinical call.

ALG5 p.Arg79Gln

c.236G>A · VCV3346143

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG5-related disorder

Computational evidence

Protein change
AlphaMissense	0.7801	likely pathogenic
REVEL	0.384	indeterminate
SaProt	LLR -13.56	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.72	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000424% European (non-Finnish) · 5/1,178,390 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000344% 5/1,455,372 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.Arg79Gln
Coding: c.236G>A
MANE Select: NM_013338
Type: single nucleotide variant
Location: chr13:36995427 (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.Arg79Trp Pathogenic same residue
ALG5 p.Arg212Cys Uncertain significance ★ ⚠ same condition
ALG5 p.Ala19Ser 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

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-arg79gln (accessed [today's date]).

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