Is ALG8 p.Ile239Thr (c.716T>C) pathogenic?

ALG8 p.Ile239Thr (c.716T>C) is classified Uncertain significance in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-18). AlphaMissense: likely benign (0.0927); Absent from gnomAD v4.1; Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Ile239Thr (c.716T>C)?

ALG8 p.Ile239Thr (c.716T>C) is associated with ALG8-congenital disorder of glycosylation, polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Ile239Thr (c.716T>C) in the general population?

ALG8 p.Ile239Thr (c.716T>C) is absent from gnomAD v4.1 (gnomAD).

How is ALG8-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG8 p.Ile239Thr (c.716T>C)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

ALG8 p.Ile239Thr

c.716T>C · VCV3574058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG8-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -8.21	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 0.44	GERP -4.3, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG8
Protein: p.Ile239Thr
Coding: c.716T>C
MANE Select: NM_024079
Type: single nucleotide variant
Location: chr11:78113947 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 239: a UniProt-annotated variant site (in pcld3)

Full ALG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG8-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: polycystic liver disease 3 with or without kidney cysts

For ALG8-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

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
ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg364Ter 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-ile239thr (accessed [today's date]).

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