Is ALG12 p.Arg120Trp (c.358C>T) pathogenic?

ALG12 p.Arg120Trp (c.358C>T) is classified Uncertain significance in ALG12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-02). AlphaMissense: likely benign (0.1146); Ultra-rare (popmax 0.0467%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG12 p.Arg120Trp (c.358C>T)?

ALG12 p.Arg120Trp (c.358C>T) is associated with Inborn genetic diseases, ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Arg120Trp (c.358C>T) in the general population?

ALG12 p.Arg120Trp (c.358C>T) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

What do computational predictors say about ALG12 p.Arg120Trp (c.358C>T)?

AlphaMissense predicts likely benign (score 0.1146) — an in-silico prediction, not a clinical call.

ALG12 p.Arg120Trp

c.358C>T · rs772004305 · VCV1351883

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1146 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1146	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.0467% Admixed American · 28/60,018 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00564% 91/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0467%	2,143
Middle Eastern	0.033%	3,031
East Asian	0.0111%	8,976
European (non-Finnish)	0.00432%	23,138
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,255

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.Arg120Trp
Coding: c.358C>T
MANE Select: NM_024105
dbSNP: rs772004305
Type: single nucleotide variant
Location: chr22:49910545 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG12-congenital disorder of glycosylation

Similar variants

ALG12 p.Arg120Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ALG12 p.Arg120= Likely benign ★ 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

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-arg120trp (accessed [today's date]).

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