Is ALG6 p.Ile159Val (c.475A>G) pathogenic?

ALG6 p.Ile159Val (c.475A>G) is classified Conflicting classifications of pathogenicity in ALG6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0983); Ultra-rare (popmax 0.0447%, eas); Associated with Inborn genetic diseases.

What condition is associated with ALG6 p.Ile159Val (c.475A>G)?

ALG6 p.Ile159Val (c.475A>G) is associated with Inborn genetic diseases, ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Ile159Val (c.475A>G) in the general population?

ALG6 p.Ile159Val (c.475A>G) is ultra-rare (popmax 0.0447%, eas) (gnomAD).

What do computational predictors say about ALG6 p.Ile159Val (c.475A>G)?

AlphaMissense predicts likely benign (score 0.0983) — an in-silico prediction, not a clinical call.

ALG6 p.Ile159Val

c.475A>G · rs531362960 · VCV1491022

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0983 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0447%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0983	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 66 kb · p 0.00074 · regional, not allelic
Overall
CADD	21.9	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 0.0447% East Asian · 20/44,698 alleles

Filtering AF 0.0296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00155% 25/1,608,524 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0447%	2,235
Remaining individualsnot grpmax-eligible	0.00802%	12,464

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: ALG6
Protein: p.Ile159Val
Coding: c.475A>G
MANE Select: NM_013339
dbSNP: rs531362960
Type: single nucleotide variant
Location: chr1:63407107 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.08

Full ALG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG6-congenital disorder of glycosylation 1C

Similar variants

ALG6 p.Ile159Thr Uncertain significance ★★ ⚠ same residue
ALG6 c.1128-1G>A Likely pathogenic ★★ same condition
ALG6 c.1128-2A>C Likely pathogenic ★★ same condition
ALG6 c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.257+5G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.429+1G>T Likely pathogenic ★★ same condition
ALG6 c.495-2A>G Likely pathogenic ★★ same condition
ALG6 c.495-2A>T 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/alg6-p-ile159val (accessed [today's date]).

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