Is STT3B p.Pro175= (c.525A>G) pathogenic?

STT3B p.Pro175= (c.525A>G) is classified Likely benign in STT3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Very rare (popmax 0.00136%, nfe); Associated with STT3B-congenital disorder of glycosylation.

What condition is associated with STT3B p.Pro175= (c.525A>G)?

STT3B p.Pro175= (c.525A>G) is associated with STT3B-congenital disorder of glycosylation (ClinVar).

How common is STT3B p.Pro175= (c.525A>G) in the general population?

STT3B p.Pro175= (c.525A>G) is very rare (popmax 0.00136%, nfe) (gnomAD).

How is STT3B-CDG inherited?

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

STT3B p.Pro175=

c.525A>G · rs749124038 · VCV2201261

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

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 0.041	phastCons 0.047
Overall
CADD	6.834	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,858 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00682% 110/1,613,822 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.144%	696
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)grpmax	0.00136%	73,741

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro175=
Coding: c.525A>G
MANE Select: NM_178862
dbSNP: rs749124038
Type: single nucleotide variant
Location: chr3:31579910 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 1 PDB
Residue 175: 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-pro175 (accessed [today's date]).

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