Is ALG1 p.Ser62= (c.186G>T) pathogenic?

ALG1 p.Ser62= (c.186G>T) is classified Likely benign in ALG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-02). Very rare (popmax 0.00787%, nfe); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Ser62= (c.186G>T)?

ALG1 p.Ser62= (c.186G>T) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Ser62= (c.186G>T) in the general population?

ALG1 p.Ser62= (c.186G>T) is very rare (popmax 0.00787%, nfe) (gnomAD).

How is ALG1-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALG1 p.Ser62=

c.186G>T · rs767351398 · VCV1597863

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00787%, nfe)

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP -4.3	GERP -2.6
Overall
CADD	5.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00787% European (non-Finnish) · 92/1,168,814 alleles

Filtering AF 0.00654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00606%

Overall 0.00616% 98/1,591,530 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00787%	12,704
Remaining individualsnot grpmax-eligible	0.0065%	15,388
African / African-American	0.00269%	37,179

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.Ser62=
Coding: c.186G>T
MANE Select: NM_019109
dbSNP: rs767351398
Type: single nucleotide variant
Location: chr16:5072035 (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-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG1 p.Ser62Ter Pathogenic ★ same residue
ALG1 p.Ser62Trp Uncertain significance ★ ⚠ same residue
ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.1187+2T>C Pathogenic ★★ same condition
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.209-2A>G Likely pathogenic ★★ same condition
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.630-2A>G Likely 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-ser62 (accessed [today's date]).

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