Is STT3B p.Pro466= (c.1398A>G) pathogenic?

STT3B p.Pro466= (c.1398A>G) is classified Likely benign in STT3B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-12-19). Rare (popmax 0.149%, mid); Associated with STT3B-congenital disorder of glycosylation.

What condition is associated with STT3B p.Pro466= (c.1398A>G)?

STT3B p.Pro466= (c.1398A>G) is associated with STT3B-congenital disorder of glycosylation (ClinVar).

How common is STT3B p.Pro466= (c.1398A>G) in the general population?

STT3B p.Pro466= (c.1398A>G) is rare (popmax 0.149%, mid) (gnomAD).

How is STT3B-CDG inherited?

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

STT3B p.Pro466=

c.1398A>G · rs143950703 · VCV387449

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Conditions

STT3B-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 -2.7	GERP -5.6
Overall
CADD	5.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.149% Middle Eastern · 9/6,058 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00849% 137/1,614,142 alleles · rare exomes 126/1,461,818 · genomes 11/152,324 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	673
Remaining individualsnot grpmax-eligible	0.0176%	5,683
South Asian	0.0165%	6,072
Admixed American	0.0117%	8,576
European (non-Finnish)	0.00797%	12,553
African / African-American	0.00133%	75,042

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: STT3B
Protein: p.Pro466=
Coding: c.1398A>G
MANE Select: NM_178862
dbSNP: rs143950703
Type: single nucleotide variant
Location: chr3:31622167 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 1 PDB
Residue 466: an α-helix

Full STT3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

STT3B-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For STT3B-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

STT3B p.Ala774Thr Uncertain significance ★★ ⚠ same condition
STT3B p.Asn789Ser Uncertain significance ★★ ⚠ same condition
STT3B p.Cys253Ser Uncertain significance ★★ same condition
STT3B p.Ser358Leu Uncertain significance ★★ ⚠ same condition
STT3B p.Val164Ile Uncertain significance ★★ ⚠ same condition
STT3B c.1172+15A>G Benign/Likely benign ★★ same condition
STT3B c.1728-18T>C Likely benign ★★ same condition
STT3B c.1900-11A>T Likely benign ★★ 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/stt3b-p-pro466 (accessed [today's date]).

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