Is ALG12 p.Arg233Gln (c.698G>A) pathogenic?

ALG12 p.Arg233Gln (c.698G>A) is classified Benign/Likely benign in ALG12 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0617); Low-frequency (popmax 1.7%, afr); Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Arg233Gln (c.698G>A)?

ALG12 p.Arg233Gln (c.698G>A) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Arg233Gln (c.698G>A) in the general population?

ALG12 p.Arg233Gln (c.698G>A) is low-frequency (popmax 1.7%, afr) (gnomAD).

How is ALG12-CDG inherited?

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

What do computational predictors say about ALG12 p.Arg233Gln (c.698G>A)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

ALG12 p.Arg233Gln

c.698G>A · rs114264124 · VCV96100

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.7%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -5.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -2.9, phastCons 0.02
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	14.89	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 1.7% African / African-American · 1,274/75,026 alleles

Filtering AF 1.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.59%

Overall 0.0939% 1,516/1,614,122 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.7%	59
Middle Eastern	0.28%	357
Admixed American	0.135%	741
Remaining individualsnot grpmax-eligible	0.102%	977
South Asian	0.00988%	10,120
European (non-Finnish)	0.00593%	16,858
East Asian	0.00223%	44,880

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: ALG12
Protein: p.Arg233Gln
Coding: c.698G>A
MANE Select: NM_024105
dbSNP: rs114264124
Type: single nucleotide variant
Location: chr22:49909314 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26

Full ALG12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG12-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG12-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG12 p.Arg233fs Pathogenic ★ same residue
ALG12 c.295+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG12 c.768+1G>A Likely pathogenic ★★ same condition
ALG12 p.Arg146Gln Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Gly101Arg Likely pathogenic ★★ same condition
ALG12 p.Thr67Met Pathogenic/Likely pathogenic ★★ same condition
ALG12 c.469+5G>A 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/alg12-p-arg233gln (accessed [today's date]).

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