Is ALG11 p.Gln318Pro (c.953A>C) pathogenic?

ALG11 p.Gln318Pro (c.953A>C) is classified Pathogenic in ALG11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-03-01). AlphaMissense: likely pathogenic (0.8533); Absent from gnomAD v4.1; Associated with ALG11-congenital disorder of glycosylation.

What condition is associated with ALG11 p.Gln318Pro (c.953A>C)?

ALG11 p.Gln318Pro (c.953A>C) is associated with ALG11-congenital disorder of glycosylation (ClinVar).

How common is ALG11 p.Gln318Pro (c.953A>C) in the general population?

ALG11 p.Gln318Pro (c.953A>C) is absent from gnomAD v4.1 (gnomAD).

How is ALG11-CDG inherited?

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

What do computational predictors say about ALG11 p.Gln318Pro (c.953A>C)?

AlphaMissense predicts likely pathogenic (score 0.8533) — an in-silico prediction, not a clinical call.

ALG11 p.Gln318Pro

c.953A>C · rs387907184 · VCV31647

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8533 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG11-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.8533	likely pathogenic ✓ concordant with ClinVar
REVEL	0.855	moderately pathogenic-leaning
SaProt	LLR -14.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	27.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG11
Protein: p.Gln318Pro
Coding: c.953A>C
MANE Select: NM_001004127
dbSNP: rs387907184
Type: single nucleotide variant
Location: chr13:52024683 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.40
Residue 318: a UniProt-annotated variant site (in cdg1p; no effect on protein expression)

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

Disease context

ALG11-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG11-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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 p.Met1Val 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

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-gln318pro (accessed [today's date]).

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