Is ALG11 p.Pro311= (c.933G>A) pathogenic?

ALG11 p.Pro311= (c.933G>A) is classified Benign in ALG11 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Common (popmax 9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with ALG11-congenital disorder of glycosylation.

What condition is associated with ALG11 p.Pro311= (c.933G>A)?

ALG11 p.Pro311= (c.933G>A) is associated with ALG11-congenital disorder of glycosylation (ClinVar).

How is ALG11-CDG inherited?

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

ALG11 p.Pro311=

Q: How common is ALG11 p.Pro311= (c.933G>A) in the general population?

ALG11 p.Pro311= (c.933G>A) is common (popmax 9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.933G>A · rs61958802 · VCV312413

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 9%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

ALG11-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.7, phastCons 0.001
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9% South Asian · 8,193/91,056 alleles

Filtering AF 8.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.77%

Overall 4.51% 72,797/1,613,952 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	9%	11
Middle Eastern	7.64%	13
Ashkenazi Jewishnot grpmax-eligible	5.13%	19
European (non-Finnish)	4.67%	21
Remaining individualsnot grpmax-eligible	4.57%	22
Finnishnot grpmax-eligible	3.06%	33
Admixed American	2.3%	44
Amishnot grpmax-eligible	1.98%	51
African / African-American	1.25%	80
East Asian	0.869%	115

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.Pro311=
Coding: c.933G>A
MANE Select: NM_001004127
dbSNP: rs61958802
Type: single nucleotide variant
Location: chr13:52024663 (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-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 p.Pro311Leu Uncertain significance ★★ ⚠ same residue
UTP14C p.Met311Thr Uncertain significance ★ ⚠ same residue
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

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-pro311 (accessed [today's date]).

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