Is ALG5 p.Arg39Gln (c.116G>A) pathogenic?

ALG5 p.Arg39Gln (c.116G>A) is classified Likely benign in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.0733); Ultra-rare (popmax 0.0148%, afr).

How common is ALG5 p.Arg39Gln (c.116G>A) in the general population?

ALG5 p.Arg39Gln (c.116G>A) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

What do computational predictors say about ALG5 p.Arg39Gln (c.116G>A)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

ALG5 p.Arg39Gln

c.116G>A · rs368291171 · VCV3111266

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -7.59	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 -5.6	GERP -4.5
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0148% African / African-American · 11/74,242 alleles

Filtering AF 0.00822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00638%

Overall 0.00212% 34/1,605,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0148%	6,749
Finnishnot grpmax-eligible	0.00469%	21,323
East Asian	0.00447%	22,382
South Asian	0.0034%	29,453
Remaining individualsnot grpmax-eligible	0.00321%	31,117
European (non-Finnish)	0.0011%	90,635

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.Arg39Gln
Coding: c.116G>A
MANE Select: NM_013338
dbSNP: rs368291171
Type: single nucleotide variant
Location: chr13:36995547 (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

Similar variants

ALG5 p.Arg39Ter Likely pathogenic ★ same residue
ALG5 p.Thr249Met Uncertain significance ★★ ⚠ same type
ALG5 c.239-2A>G Likely pathogenic ★ same type
ALG5 p.Arg97Ter Pathogenic ★ same type
ALG5 p.Trp224Ter Likely pathogenic ★ same type
ALG5 p.Ala14Thr Uncertain significance ★ ⚠ same type
ALG5 p.Ala16Ser Uncertain significance ★ ⚠ same type
ALG5 p.Ala17Val Uncertain significance ★ ⚠ same type

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-arg39gln (accessed [today's date]).

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