Is ALG1 p.Cys390= (c.1170T>C) pathogenic?

ALG1 p.Cys390= (c.1170T>C) is classified Likely benign in ALG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-15). Very rare (popmax 0.00956%, afr); Associated with ALG1-related disorder.

What condition is associated with ALG1 p.Cys390= (c.1170T>C)?

ALG1 p.Cys390= (c.1170T>C) is associated with ALG1-related disorder (ClinVar).

How common is ALG1 p.Cys390= (c.1170T>C) in the general population?

ALG1 p.Cys390= (c.1170T>C) is very rare (popmax 0.00956%, afr) (gnomAD).

ALG1 p.Cys390=

c.1170T>C · rs80210219 · VCV3033829

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00956%, afr)

Conditions

ALG1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor gain, 17 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -13	GERP -3.3
Overall
CADD	0.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00956% African / African-American · 7/73,254 alleles

Filtering AF 0.00446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.00214% 34/1,591,560 alleles · very rare exomes 34/1,439,248 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00956%	10,465
Ashkenazi Jewishnot grpmax-eligible	0.00681%	14,681
East Asian	0.00453%	22,086
European (non-Finnish)	0.0018%	55,455
Admixed American	0.00167%	59,930
Finnishnot grpmax-eligible	0.00157%	63,680

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.Cys390=
Coding: c.1170T>C
MANE Select: NM_019109
dbSNP: rs80210219
Type: single nucleotide variant
Location: chr16:5082656 (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

ALG1-related disorder

Similar variants

ALG1 p.Cys390Ter Pathogenic ★ same residue
ALG1 p.Cys390Gly Uncertain significance ★ ⚠ same residue
ALG1 p.Ser258Leu Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Tyr113Ter Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Arg247His Likely pathogenic ★ ⚠ same condition
ALG1 c.1187+3A>G Conflicting classifications of pathogenicity ★ same condition
ALG1 c.*5T>C Likely benign same condition
ALG1 p.Glu275= 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/alg1-p-cys390 (accessed [today's date]).

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