Is ALG1 p.Asp429Glu (c.1287T>A) pathogenic?

ALG1 p.Asp429Glu (c.1287T>A) is classified Benign in ALG1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1485); Common (popmax 16.1%, amr) — too common for a highly-penetrant pathogenic allele; Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Asp429Glu (c.1287T>A)?

ALG1 p.Asp429Glu (c.1287T>A) 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.

What do computational predictors say about ALG1 p.Asp429Glu (c.1287T>A)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

ALG1 p.Asp429Glu

Q: How common is ALG1 p.Asp429Glu (c.1287T>A) in the general population?

ALG1 p.Asp429Glu (c.1287T>A) is common (popmax 16.1%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1287T>A · rs9745522 · VCV194258

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 16.1%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -1, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	13.82	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 16.1% Admixed American · 9,644/59,974 alleles

Filtering AF 15.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.7%

Overall 10.5% 167,349/1,595,586 alleles · common exomes 149,359/1,443,410 · genomes 17,990/152,176 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	16.8%	6
Admixed Americangrpmax	16.1%	6
African / African-American	14.1%	7
South Asian	13.7%	7
Finnishnot grpmax-eligible	12.4%	8
Middle Eastern	12.1%	8
Remaining individualsnot grpmax-eligible	10.4%	10
European (non-Finnish)	9.77%	10
East Asian	8.62%	12
Ashkenazi Jewishnot grpmax-eligible	8.39%	12

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp429Glu
Coding: c.1287T>A
MANE Select: NM_019109
dbSNP: rs9745522
Type: single nucleotide variant
Location: chr16:5084773 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24
Residue 429: a UniProt-annotated variant site (no effect on 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

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.Asp429= Likely benign ★ 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
ALG1 c.863-2A>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-asp429glu (accessed [today's date]).

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