Is ALG1 p.Arg28Gln (c.83G>A) pathogenic?

ALG1 p.Arg28Gln (c.83G>A) is classified Likely benign in ALG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.0962); Very rare (popmax 6.96e-05%); Associated with intellectual disability.

What condition is associated with ALG1 p.Arg28Gln (c.83G>A)?

ALG1 p.Arg28Gln (c.83G>A) is associated with intellectual disability (ClinVar).

How common is ALG1 p.Arg28Gln (c.83G>A) in the general population?

ALG1 p.Arg28Gln (c.83G>A) is very rare (popmax 6.96e-05%) (gnomAD).

What do computational predictors say about ALG1 p.Arg28Gln (c.83G>A)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

ALG1 p.Arg28Gln

c.83G>A · rs1353988508 · VCV975486

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.96e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.83	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 1.2	GERP 1.1, phastCons 0.034
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	16.11	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 6.96e-05%

Overall 6.96e-05% 1/1,436,868 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: ALG1
Protein: p.Arg28Gln
Coding: c.83G>A
MANE Select: NM_019109
dbSNP: rs1353988508
Type: single nucleotide variant
Location: chr16:5071932 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG1 p.Lys72Arg Likely benign same condition
ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same type
ALG1 c.1187+2T>C Pathogenic ★★ same type
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same type
ALG1 c.209-2A>G Likely pathogenic ★★ same type
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same type
ALG1 c.630-2A>G Likely pathogenic ★★ same type
ALG1 c.863-2A>G Likely pathogenic ★★ 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/alg1-p-arg28gln (accessed [today's date]).

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