Is ALG11 p.Met1Val (c.1A>G) pathogenic?

ALG11 p.Met1Val (c.1A>G) is classified Likely pathogenic in ALG11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-23). Very rare (popmax 6.2e-05%); Associated with ALG11-related disorder.

What condition is associated with ALG11 p.Met1Val (c.1A>G)?

ALG11 p.Met1Val (c.1A>G) is associated with ALG11-related disorder, ALG11-congenital disorder of glycosylation (ClinVar).

How common is ALG11 p.Met1Val (c.1A>G) in the general population?

ALG11 p.Met1Val (c.1A>G) is very rare (popmax 6.2e-05%) (gnomAD).

ALG11 p.Met1Val

c.1A>G · rs921941078 · VCV1028907

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

ALG11-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.502	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,170 alleles · very rare exomes 1/1,461,810 · genomes 0/152,360 · 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: ALG11
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_001004127
dbSNP: rs921941078
Type: single nucleotide variant
Location: chr13:52012419 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.40

Full ALG11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG11-related disorder

Also linked: ALG11-congenital disorder of glycosylation

Similar variants

ALG11 c.45-2A>T Likely pathogenic ★★ same condition
ALG11 p.Arg468Cys Likely pathogenic ★★ ⚠ same condition
ALG11 p.Arg468His Likely pathogenic ★★ same condition
ALG11 c.*540T>A Uncertain significance ★★ ⚠ same condition
ALG11 p.Arg136Cys Uncertain significance ★★ same condition
ALG11 p.Arg15Thr Uncertain significance ★★ ⚠ same condition
ALG11 p.Arg346His Uncertain significance ★★ ⚠ same condition
ALG11 p.Asn257Ser Uncertain significance ★★ ⚠ 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/alg11-p-met1val (accessed [today's date]).

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