Is ALG1 p.Phe427= (c.1281T>C) pathogenic?

ALG1 p.Phe427= (c.1281T>C) is classified Likely benign in ALG1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0333%, amr); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Phe427= (c.1281T>C)?

ALG1 p.Phe427= (c.1281T>C) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Phe427= (c.1281T>C) in the general population?

ALG1 p.Phe427= (c.1281T>C) is ultra-rare (popmax 0.0333%, amr) (gnomAD).

How is ALG1-CDG inherited?

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

ALG1 p.Phe427=

c.1281T>C · rs538385814 · VCV382966

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

Conditions

ALG1-congenital disorder of glycosylation

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.052	GERP -1.7, phastCons 0.9
Overall
CADD	5.624	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% Admixed American · 20/60,010 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00251% 40/1,596,426 alleles · ultra-rare exomes 19/1,444,134 · genomes 21/152,292 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0333%	3,000
African / African-American	0.00934%	10,709
Remaining individualsnot grpmax-eligible	0.00482%	20,740
East Asian	0.00223%	44,880
European (non-Finnish)	0.000763%	131,085

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.Phe427=
Coding: c.1281T>C
MANE Select: NM_019109
dbSNP: rs538385814
Type: single nucleotide variant
Location: chr16:5084767 (GRCh38)

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

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-phe427 (accessed [today's date]).

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