Is ALG1 p.Arg438Trp (c.1312C>T) pathogenic?

ALG1 p.Arg438Trp (c.1312C>T) is classified Pathogenic in ALG1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-13). AlphaMissense: likely benign (0.1823); Very rare (popmax 0.00333%, amr); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Arg438Trp (c.1312C>T)?

ALG1 p.Arg438Trp (c.1312C>T) is associated with ALG1-congenital disorder of glycosylation, congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Arg438Trp (c.1312C>T) in the general population?

ALG1 p.Arg438Trp (c.1312C>T) is very rare (popmax 0.00333%, amr) (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.Arg438Trp (c.1312C>T)?

AlphaMissense predicts likely benign (score 0.1823) — an in-silico prediction, not a clinical call.

ALG1 p.Arg438Trp

c.1312C>T · rs16835020 · VCV690315

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1823	likely benign ⚠ discordant with ClinVar
REVEL	0.619	indeterminate
SaProt	LLR -12.45	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 0.82, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	24.5	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 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00094% 15/1,596,316 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
Remaining individualsnot grpmax-eligible	0.00161%	62,198
European (non-Finnish)	0.00102%	98,316

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.Arg438Trp
Coding: c.1312C>T
MANE Select: NM_201400 · reported on NM_019109
dbSNP: rs16835020
Type: single nucleotide variant
Location: chr16:5084798 (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

Also linked: congenital disorder of glycosylation

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-arg438trp (accessed [today's date]).

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