Is ALG1 p.Arg263Trp (c.787C>T) pathogenic?

ALG1 p.Arg263Trp (c.787C>T) is classified Conflicting classifications of pathogenicity in ALG1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-30). AlphaMissense: likely benign (0.0962); Rare (popmax 0.221%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Arg263Trp (c.787C>T)?

ALG1 p.Arg263Trp (c.787C>T) is associated with Inborn genetic diseases, ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Arg263Trp (c.787C>T) in the general population?

ALG1 p.Arg263Trp (c.787C>T) is rare (popmax 0.221%, afr) (gnomAD).

What do computational predictors say about ALG1 p.Arg263Trp (c.787C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

ALG1 p.Arg263Trp

c.787C>T · rs145317306 · VCV798144

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.221%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -12.07	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -2.8
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	12.74	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 0.221% African / African-American · 166/75,006 alleles

Filtering AF 0.194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.183%

Overall 0.0146% 236/1,612,800 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.221%	452
Admixed American	0.0816%	1,225
Middle Eastern	0.0192%	5,198
Remaining individualsnot grpmax-eligible	0.016%	6,239
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
South Asian	0.0011%	91,020
European (non-Finnish)	0.000678%	147,476

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.Arg263Trp
Coding: c.787C>T
MANE Select: NM_019109
dbSNP: rs145317306
Type: single nucleotide variant
Location: chr16:5078803 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG1-congenital disorder of glycosylation

Similar variants

ALG1 p.Arg263Gln 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
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-arg263trp (accessed [today's date]).

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