Is ALG8 p.Phe153= (c.459C>T) pathogenic?

ALG8 p.Phe153= (c.459C>T) is classified Likely benign in ALG8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.055%, amr); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Phe153= (c.459C>T)?

ALG8 p.Phe153= (c.459C>T) is associated with ALG8-congenital disorder of glycosylation (ClinVar).

How common is ALG8 p.Phe153= (c.459C>T) in the general population?

ALG8 p.Phe153= (c.459C>T) is ultra-rare (popmax 0.055%, amr) (gnomAD).

How is ALG8-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALG8 p.Phe153=

c.459C>T · rs144501219 · VCV752216

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.055%, amr)

Conditions

ALG8-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.295	indeterminate
Splicing
SpliceAI	Δ0.34	donor loss, 19 bp away · masked 0 · deltas
Pangolin	Δ0.34	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.75	GERP -4.6
Overall
CADD	4.679	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.055% Admixed American · 33/59,998 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.0149% 240/1,613,622 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.055%	1,818
European (non-Finnish)	0.0161%	6,209
Remaining individualsnot grpmax-eligible	0.008%	12,496
South Asian	0.00659%	15,178
East Asian	0.00446%	22,421
African / African-American	0.004%	25,008
Finnishnot grpmax-eligible	0.00157%	63,850

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.Phe153=
Coding: c.459C>T
MANE Select: NM_024079
dbSNP: rs144501219
Type: single nucleotide variant
Location: chr11:78121084 (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

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-phe153 (accessed [today's date]).

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