Is ALG1 p.Ala3Asp (c.8C>A) pathogenic?

ALG1 p.Ala3Asp (c.8C>A) is classified Benign/Likely benign in ALG1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.2391); Rare (popmax 0.625%, sas); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Ala3Asp (c.8C>A)?

ALG1 p.Ala3Asp (c.8C>A) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Ala3Asp (c.8C>A) in the general population?

ALG1 p.Ala3Asp (c.8C>A) is rare (popmax 0.625%, sas) (gnomAD).

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.Ala3Asp (c.8C>A)?

AlphaMissense predicts likely benign (score 0.2391) — an in-silico prediction, not a clinical call.

ALG1 p.Ala3Asp

c.8C>A · rs559805054 · VCV1669865

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2391 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.625%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2391	likely benign
REVEL	0.402	indeterminate
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP 0.14
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	18.04	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 0.625% South Asian · 566/90,610 alleles

Filtering AF 0.582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.565%

Overall 0.0403% 646/1,604,626 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.625%	160
Ashkenazi Jewishnot grpmax-eligible	0.0644%	1,553
Middle Eastern	0.0536%	1,866
Remaining individualsnot grpmax-eligible	0.0386%	2,592
Admixed American	0.00335%	29,888
European (non-Finnish)	0.00263%	38,030
Finnishnot grpmax-eligible	0.00174%	57,356

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.Ala3Asp
Coding: c.8C>A
MANE Select: NM_019109
dbSNP: rs559805054
Type: single nucleotide variant
Location: chr16:5071857 (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.Ala3= Likely benign ★ same residue
ALG1 p.Ala3Thr 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-ala3asp (accessed [today's date]).

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