Is ALG8 p.Ile52Val (c.154A>G) pathogenic?

ALG8 p.Ile52Val (c.154A>G) is classified Conflicting classifications of pathogenicity in ALG8 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-28). AlphaMissense: likely benign (0.0551); Rare (popmax 0.847%, eas); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Ile52Val (c.154A>G)?

ALG8 p.Ile52Val (c.154A>G) is associated with ALG8-congenital disorder of glycosylation, polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Ile52Val (c.154A>G) in the general population?

ALG8 p.Ile52Val (c.154A>G) is rare (popmax 0.847%, eas) (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.Ile52Val (c.154A>G)?

AlphaMissense predicts likely benign (score 0.0551) — an in-silico prediction, not a clinical call.

ALG8 p.Ile52Val

c.154A>G · rs138293432 · VCV728679

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0551 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.847%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG8-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0551	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.8
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	0.061	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.847% East Asian · 380/44,876 alleles

Filtering AF 0.777% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.749%

Overall 0.0361% 582/1,613,922 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.847%	118
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.0151%	6,628
Admixed American	0.00833%	12,002
African / African-American	0.00266%	37,527
South Asian	0.0022%	45,535

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
Protein: p.Ile52Val
Coding: c.154A>G
MANE Select: NM_024079
dbSNP: rs138293432
Type: single nucleotide variant
Location: chr11:78127378 (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-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-ile52val (accessed [today's date]).

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