Is ALG1 p.Ile209Ser (c.626T>G) pathogenic?

ALG1 p.Ile209Ser (c.626T>G) is classified Likely pathogenic in ALG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-05-25). AlphaMissense: likely pathogenic (0.863); Very rare (popmax 0.0011%, sas); Associated with congenital disorder of glycosylation.

What condition is associated with ALG1 p.Ile209Ser (c.626T>G)?

ALG1 p.Ile209Ser (c.626T>G) is associated with congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Ile209Ser (c.626T>G) in the general population?

ALG1 p.Ile209Ser (c.626T>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ALG1 p.Ile209Ser (c.626T>G)?

AlphaMissense predicts likely pathogenic (score 0.863) — an in-silico prediction, not a clinical call.

ALG1 p.Ile209Ser

c.626T>G · rs1596256204 · VCV690324

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.863 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.863	likely pathogenic ✓ concordant with ClinVar
REVEL	0.731	pathogenic-leaning
SaProt	LLR -11.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	25.8	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 0.0011% South Asian · 1/91,082 alleles

Overall 0.000137% 2/1,461,828 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	8.47e-05%	1,179,998

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.Ile209Ser
Coding: c.626T>G
MANE Select: NM_019109
dbSNP: rs1596256204
Type: single nucleotide variant
Location: chr16:5077531 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24
Residue 209: a UniProt-annotated variant site (in cdg1k; decreased function in protein glycosylation as shown by rescue assays in an alg1-deficient yeast strain)

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

Disease context

congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Ala360Val Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Arg276Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG1 p.Asp289Gly Likely pathogenic ★★ same condition
ALG1 p.Cys5Ter Pathogenic ★★ same condition
ALG1 p.Ser258Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG1 p.Ser359Leu Pathogenic ★★ ⚠ 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-ile209ser (accessed [today's date]).

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