Is ST3GAL3 p.Arg366= (c.1098C>T) pathogenic?

ST3GAL3 p.Arg366= (c.1098C>T) is classified Likely benign in ST3GAL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-02). Ultra-rare (popmax 0.0337%, mid); Associated with early-infantile DEE.

What condition is associated with ST3GAL3 p.Arg366= (c.1098C>T)?

ST3GAL3 p.Arg366= (c.1098C>T) is associated with early-infantile DEE (ClinVar).

How common is ST3GAL3 p.Arg366= (c.1098C>T) in the general population?

ST3GAL3 p.Arg366= (c.1098C>T) is ultra-rare (popmax 0.0337%, mid) (gnomAD).

ST3GAL3 p.Arg366=

c.1098C>T · rs373494209 · VCV1537916

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, mid)

Conditions

early-infantile DEE

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.201	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -3.8
Overall
CADD	1.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0337% Middle Eastern · 2/5,932 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00112% 18/1,613,868 alleles · ultra-rare exomes 16/1,461,648 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0337%	2,966
Admixed American	0.00667%	15,001
South Asian	0.00659%	15,180
Remaining individualsnot grpmax-eligible	0.0016%	62,460
European (non-Finnish)	0.000424%	236,011

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: ST3GAL3
Protein: p.Arg366=
Coding: c.1098C>T
MANE Select: NM_006279
dbSNP: rs373494209
Type: single nucleotide variant
Location: chr1:43930191 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 90.87

Full ST3GAL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

early-infantile DEE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ST3GAL3 p.Arg366His Uncertain significance ★★ ⚠ same residue
ST3GAL3 c.166+1G>A Pathogenic/Likely pathogenic ★★ same condition
ST3GAL3 p.Arg261Ter Pathogenic/Likely pathogenic ★★ same condition
ST3GAL3 c.118+5G>A Uncertain significance ★★ same condition
ST3GAL3 c.397+6T>G Uncertain significance ★★ same condition
ST3GAL3 p.Ala281Thr Uncertain significance ★★ ⚠ same condition
ST3GAL3 p.Arg115Leu Uncertain significance ★★ ⚠ same condition
ST3GAL3 p.Arg147His 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/st3gal3-p-arg366 (accessed [today's date]).

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