Is ALG12 p.Ile393Val (c.1177A>G) pathogenic?

ALG12 p.Ile393Val (c.1177A>G) is classified Benign in ALG12 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0863); Common (popmax 19.9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Ile393Val (c.1177A>G)?

ALG12 p.Ile393Val (c.1177A>G) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

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.Ile393Val (c.1177A>G)?

AlphaMissense predicts likely benign (score 0.0863) — an in-silico prediction, not a clinical call.

ALG12 p.Ile393Val

Q: How common is ALG12 p.Ile393Val (c.1177A>G) in the general population?

ALG12 p.Ile393Val (c.1177A>G) is common (popmax 19.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1177A>G · rs3922872 · VCV96095

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0863 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 19.9%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0863	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -7.05	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 2.7	GERP 0.67, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	21.3	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 19.9% South Asian · 18,105/91,070 alleles

Filtering AF 19.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.5%

Overall 11.4% 183,749/1,614,008 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	19.9%	5
Amishnot grpmax-eligible	17.4%	6
Ashkenazi Jewishnot grpmax-eligible	14.6%	7
Finnishnot grpmax-eligible	12.5%	8
European (non-Finnish)	11.5%	9
Remaining individualsnot grpmax-eligible	11.2%	9
Middle Eastern	9.83%	10
Admixed American	7.54%	13
East Asian	4.76%	21
African / African-American	4.39%	23

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.Ile393Val
Coding: c.1177A>G
MANE Select: NM_024105
dbSNP: rs3922872
Type: single nucleotide variant
Location: chr22:49904240 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26
Residue 393: a UniProt-annotated variant site (in)

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 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
ALG12 c.470-3C>T 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-ile393val (accessed [today's date]).

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