Is ALG1 p.Val96= (c.288T>C) pathogenic?

ALG1 p.Val96= (c.288T>C) is classified Likely benign in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-04). Very rare (popmax 0.00549%, sas); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Val96= (c.288T>C)?

ALG1 p.Val96= (c.288T>C) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Val96= (c.288T>C) in the general population?

ALG1 p.Val96= (c.288T>C) is very rare (popmax 0.00549%, sas) (gnomAD).

How is ALG1-CDG inherited?

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

ALG1 p.Val96=

c.288T>C · rs1238229639 · VCV2765053

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.4	GERP 0.42
Overall
CADD	8.694	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,092 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00031% 5/1,614,086 alleles · very rare exomes 4/1,461,886 · genomes 1/152,200 · joint denominator

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: ALG1
Protein: p.Val96=
Coding: c.288T>C
MANE Select: NM_019109
dbSNP: rs1238229639
Type: single nucleotide variant
Location: chr16:5073154 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG1 p.Val96Ala Uncertain significance ★ ⚠ same residue
ALG1 p.Val96Asp Uncertain significance ★ ⚠ same residue
ALG1 p.Val96Gly Uncertain significance ★ ⚠ same residue
ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.1187+2T>C Pathogenic ★★ same condition
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.209-2A>G Likely pathogenic ★★ same condition
ALG1 c.539+1G>A 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/alg1-p-val96 (accessed [today's date]).

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