Is ALG11 p.Cys345Phe (c.1034G>T) pathogenic?

ALG11 p.Cys345Phe (c.1034G>T) is classified Uncertain significance in ALG11 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.6306); Very rare (popmax 0.00133%, afr); Associated with ALG11-congenital disorder of glycosylation.

What condition is associated with ALG11 p.Cys345Phe (c.1034G>T)?

ALG11 p.Cys345Phe (c.1034G>T) is associated with ALG11-congenital disorder of glycosylation (ClinVar).

How common is ALG11 p.Cys345Phe (c.1034G>T) in the general population?

ALG11 p.Cys345Phe (c.1034G>T) is very rare (popmax 0.00133%, afr) (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.Cys345Phe (c.1034G>T)?

AlphaMissense predicts likely pathogenic (score 0.6306) — an in-silico prediction, not a clinical call.

ALG11 p.Cys345Phe

c.1034G>T · rs886050313 · VCV312415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6306 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG11-congenital disorder of glycosylation

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.6306	likely pathogenic
REVEL	0.722	pathogenic-leaning
SaProt	LLR -15.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,950 alleles

Overall 0.000124% 2/1,614,120 alleles · very rare exomes 1/1,461,870 · genomes 1/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,950
European (non-Finnish)	8.47e-05%	1,180,043

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.Cys345Phe
Coding: c.1034G>T
MANE Select: NM_001004127
dbSNP: rs886050313
Type: single nucleotide variant
Location: chr13:52024764 (GRCh38)

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

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-cys345phe (accessed [today's date]).

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