Is ALG8 p.Phe235fs (c.705del) pathogenic?

ALG8 p.Phe235fs (c.705del) is classified Likely pathogenic in ALG8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-31). Absent from gnomAD v4.1; Associated with ALG8-related disorder.

What condition is associated with ALG8 p.Phe235fs (c.705del)?

ALG8 p.Phe235fs (c.705del) is associated with ALG8-related disorder (ClinVar).

How common is ALG8 p.Phe235fs (c.705del) in the general population?

ALG8 p.Phe235fs (c.705del) is absent from gnomAD v4.1 (gnomAD).

ALG8 p.Phe235fs

c.705del · VCV3347517

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,974)

Conditions

ALG8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.7	GERP -4.3

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,602,974). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALG8
Protein: p.Phe235fs
Coding: c.705del
MANE Select: NM_024079
Type: Deletion
Location: chr11:78113958 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 235: a UniProt-annotated variant site (in pcld3)

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 c.898+1G>T Likely pathogenic same condition
ALG8 p.Phe406_Leu407insTer Pathogenic same condition
ALG8 p.Phe143Cys 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-phe235fs (accessed [today's date]).

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