Is ALG1 p.Phe383= (c.1149C>T) pathogenic?

ALG1 p.Phe383= (c.1149C>T) is classified Benign in ALG1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 65.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Phe383= (c.1149C>T)?

ALG1 p.Phe383= (c.1149C>T) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How is ALG1-CDG inherited?

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

ALG1 p.Phe383=

Q: How common is ALG1 p.Phe383= (c.1149C>T) in the general population?

ALG1 p.Phe383= (c.1149C>T) is common (popmax 65.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1149C>T · rs1047732 · VCV95932

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 65.4%, sas) — too common for a highly-penetrant pathogenic allele

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	Δ0.39	donor loss · deltas
Pangolin	Δ0.20	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -5.6	GERP -3.3
Overall
CADD	0.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 65.4% South Asian · 59,491/90,910 alleles

Filtering AF 65% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.8%

Overall 52.2% 840,420/1,610,746 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	65.4%	2
East Asian	62.3%	2
Finnishnot grpmax-eligible	56.3%	2
Remaining individualsnot grpmax-eligible	52.2%	2
European (non-Finnish)	52%	2
Amishnot grpmax-eligible	51.3%	2
Middle Eastern	46.8%	2
Ashkenazi Jewishnot grpmax-eligible	46%	2
African / African-American	40.9%	2
Admixed American	40.7%	2

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.Phe383=
Coding: c.1149C>T
MANE Select: NM_019109
dbSNP: rs1047732
Type: single nucleotide variant
Location: chr16:5082635 (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 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
ALG1 c.863-2A>G Likely pathogenic ★★ same condition
ALG1 c.961+1G>A 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-phe383 (accessed [today's date]).

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