Is ALG8 c.898+1G>T pathogenic?

ALG8 c.898+1G>T is classified Likely pathogenic in ALG8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-11). Very rare (popmax 0.00017%, nfe); Associated with ALG8-related disorder.

What condition is associated with ALG8 c.898+1G>T?

ALG8 c.898+1G>T is associated with ALG8-related disorder (ClinVar).

How common is ALG8 c.898+1G>T in the general population?

ALG8 c.898+1G>T is very rare (popmax 0.00017%, nfe) (gnomAD).

ALG8 c.898+1G>T

VCV3347910

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

ALG8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
REVEL	0.435	indeterminate
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.93	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.76	loss · gain 0.25 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Non-coding constraint	Z -2.63	1 kb window · o/e 1.21 · regional · uncalibrated
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,738 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,424 alleles · very rare

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
Coding: c.898+1G>T
MANE Select: NM_024079
Type: single nucleotide variant
Location: chr11:78112649 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07

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

Disease context

ALG8-related disorder

Similar variants

ALG8 c.777+1G>A Likely pathogenic ★★ same condition
ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Pro425Gln Uncertain significance ★★ ⚠ same condition
ALG8 p.Tyr463Cys Uncertain significance ★ ⚠ same condition
ALG8 p.Phe143Cys Uncertain significance ⚠ same condition
ALG8 p.Asp86= Likely benign same condition
ALG8 p.Ser404= Likely benign 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-c-898-plus-1g-t (accessed [today's date]).

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