Is ALG8 c.777+24del pathogenic?

ALG8 c.777+24del is classified Benign in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-26). Common (popmax 24%, mid) — too common for a highly-penetrant pathogenic allele.

ALG8 c.777+24del

Q: How common is ALG8 c.777+24del in the general population?

ALG8 c.777+24del is common (popmax 24%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

VCV4683665

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 24%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +24	near-intronic (+24 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP -3.5
Overall
CADD	0.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24% Middle Eastern · 1,141/4,746 alleles

Filtering AF 22.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.7%

Overall 21.7% 252,232/1,162,350 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	24.8%	4
Middle Easterngrpmax	24%	4
Ashkenazi Jewishnot grpmax-eligible	24%	4
European (non-Finnish)	22.8%	4
Remaining individualsnot grpmax-eligible	21.7%	5
Admixed American	20.4%	5
South Asian	20.3%	5
East Asian	16.5%	6
African / African-American	3.8%	26

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.777+24del
MANE Select: NM_024079
Type: Deletion
Location: chr11:78113862 (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

Similar variants

ALG8 p.Arg268fs Pathogenic/Likely pathogenic ★★ same type
ALG8 p.Asn91fs Pathogenic/Likely pathogenic ★★ same type
ALG8 p.Gly275fs Pathogenic/Likely pathogenic ★★ same type
ALG8 p.Trp353fs Likely pathogenic ★★ same type
ALG8 c.174+30del Benign ★★ same type
ALG8 c.174+2del Likely pathogenic ★ same type
ALG8 p.Thr367fs Pathogenic ★ same type
ALG8 p.Trp378fs Likely pathogenic ★ same type

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-777-plus-24del (accessed [today's date]).

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