Is ALG5 p.Arg309Gln (c.926G>A) pathogenic?

ALG5 p.Arg309Gln (c.926G>A) is classified Uncertain significance in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.2692); Very rare (popmax 0.00335%, amr).

How common is ALG5 p.Arg309Gln (c.926G>A) in the general population?

ALG5 p.Arg309Gln (c.926G>A) is very rare (popmax 0.00335%, amr) (gnomAD).

What do computational predictors say about ALG5 p.Arg309Gln (c.926G>A)?

AlphaMissense predicts likely benign (score 0.2692) — an in-silico prediction, not a clinical call.

ALG5 p.Arg309Gln

c.926G>A · rs370016246 · VCV2211105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2692	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -6.79	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 2.2	GERP 2.1, phastCons 0.98
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	26.0	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 0.00335% Admixed American · 2/59,740 alleles

Filtering AF 0.000555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.00062% 10/1,613,246 alleles · very rare exomes 8/1,461,092 · genomes 2/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00335%	29,870
African / African-American	0.00134%	74,884
European (non-Finnish)	0.000593%	168,544

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.Arg309Gln
Coding: c.926G>A
MANE Select: NM_013338
dbSNP: rs370016246
Type: single nucleotide variant
Location: chr13:36949991 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29
Residue 309: a UniProt-annotated variant site (in pkd7)

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

Similar variants

ALG5 p.Arg309Leu Uncertain significance ★ ⚠ same residue
ALG5 p.Arg309Ter Uncertain significance ★ same residue
ALG5 p.Thr249Met Uncertain significance ★★ ⚠ same type
ALG5 c.239-2A>G Likely pathogenic ★ same type
ALG5 p.Arg39Ter Likely pathogenic ★ same type
ALG5 p.Arg97Ter Pathogenic ★ same type
ALG5 p.Trp224Ter Likely pathogenic ★ same type
ALG5 p.Ala14Thr 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-arg309gln (accessed [today's date]).

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