Is ALG8 p.Thr481Ile (c.1442C>T) pathogenic?

ALG8 p.Thr481Ile (c.1442C>T) is classified Uncertain significance in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.2743); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG8 p.Thr481Ile (c.1442C>T)?

ALG8 p.Thr481Ile (c.1442C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG8 p.Thr481Ile (c.1442C>T) in the general population?

ALG8 p.Thr481Ile (c.1442C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG8 p.Thr481Ile (c.1442C>T)?

AlphaMissense predicts likely benign (score 0.2743) — an in-silico prediction, not a clinical call.

ALG8 p.Thr481Ile

c.1442C>T · rs1859775779 · VCV3111369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2743 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2743	likely benign
REVEL	0.37	indeterminate
SaProt	LLR -8.41	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 3.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	17.5	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.Thr481Ile
Coding: c.1442C>T
MANE Select: NM_024079
dbSNP: rs1859775779
Type: single nucleotide variant
Location: chr11:78101103 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 481: a UniProt-annotated variant site (in pcld3)

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

Similar variants

ALG8 p.Thr481= Likely benign ★ same residue
ALG8 p.Ala250Val Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala388Pro Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala403Thr Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala424Val Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala72Val Uncertain significance ★★ ⚠ same condition
ALG8 p.Arg215Gln Uncertain significance ★★ ⚠ same condition
ALG8 p.Gly130Glu Uncertain significance ★★ ⚠ 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-thr481ile (accessed [today's date]).

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