Is ALG1 p.Arg30Trp (c.88C>T) pathogenic?

ALG1 p.Arg30Trp (c.88C>T) is classified Uncertain significance in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.1382); Very rare (popmax 8.57e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Arg30Trp (c.88C>T)?

ALG1 p.Arg30Trp (c.88C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG1 p.Arg30Trp (c.88C>T) in the general population?

ALG1 p.Arg30Trp (c.88C>T) is very rare (popmax 8.57e-05%, nfe) (gnomAD).

What do computational predictors say about ALG1 p.Arg30Trp (c.88C>T)?

AlphaMissense predicts likely benign (score 0.1382) — an in-silico prediction, not a clinical call.

ALG1 p.Arg30Trp

c.88C>T · VCV4037627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1382 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1382	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -11.74	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.19, phastCons 0.011
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	20.7	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 8.57e-05% European (non-Finnish) · 1/1,167,432 alleles

Overall 6.3e-05% 1/1,587,734 alleles · very rare exomes 1/1,435,424 · genomes 0/152,310 · joint denominator

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.Arg30Trp
Coding: c.88C>T
MANE Select: NM_019109
Type: single nucleotide variant
Location: chr16:5071937 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG1 p.Arg30= Likely benign ★ same residue
ALG1 p.Ala360Val Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Gln342Pro Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Ala278Thr Uncertain significance ★★ same condition
ALG1 p.Arg257Gln Uncertain significance ★★ ⚠ same condition
ALG1 p.Asn311Lys Uncertain significance ★★ ⚠ same condition
ALG1 p.Asn80His Uncertain significance ★★ ⚠ same condition
ALG1 p.Asp252Glu Uncertain significance ★★ ⚠ 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/alg1-p-arg30trp (accessed [today's date]).

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