Is ALG8 p.Thr47Ser (c.139A>T) pathogenic?

ALG8 p.Thr47Ser (c.139A>T) is classified Uncertain significance in ALG8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-02). AlphaMissense: ambiguous (0.548); Very rare (popmax 0.00212%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG8 p.Thr47Ser (c.139A>T)?

ALG8 p.Thr47Ser (c.139A>T) is associated with Inborn genetic diseases, ALG8-congenital disorder of glycosylation, polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Thr47Ser (c.139A>T) in the general population?

ALG8 p.Thr47Ser (c.139A>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about ALG8 p.Thr47Ser (c.139A>T)?

AlphaMissense predicts ambiguous (score 0.548) — an in-silico prediction, not a clinical call.

ALG8 p.Thr47Ser

c.139A>T · rs121908293 · VCV2346358

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.548	ambiguous
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -11.37	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	25.1	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 0.00212% European (non-Finnish) · 25/1,179,922 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00161% 26/1,613,600 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,197
African / African-American	0.00133%	74,912

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: ALG8
Protein: p.Thr47Ser
Coding: c.139A>T
MANE Select: NM_024079
dbSNP: rs121908293
Type: single nucleotide variant
Location: chr11:78127393 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 47: a UniProt-annotated variant site (in cdg1h; decreased dolichyl pyrophosphate glc1man9glcnac2 alpha-1,3-glucosyltransferase activity)

Full ALG8 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: ALG8-congenital disorder of glycosylation polycystic liver disease 3 with or without kidney cysts

Similar variants

ALG8 p.Thr47Pro Pathogenic ★ same residue
ALG8 p.Thr47= Likely benign ★ same residue
ALG8 c.368+2T>G Likely pathogenic ★★ same condition
ALG8 c.674-2A>G Likely pathogenic ★★ same condition
ALG8 c.777+1G>A Likely pathogenic ★★ same condition
ALG8 c.95+1G>A Likely pathogenic ★★ same condition
ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg229Ter Pathogenic/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/alg8-p-thr47ser (accessed [today's date]).

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