Is SLC35A2 p.Pro365= (c.1095C>T) pathogenic?

SLC35A2 p.Pro365= (c.1095C>T) is classified Likely benign in SLC35A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). Very rare (popmax 0.00437%, amr); Associated with SLC35A2-congenital disorder of glycosylation.

What condition is associated with SLC35A2 p.Pro365= (c.1095C>T)?

SLC35A2 p.Pro365= (c.1095C>T) is associated with SLC35A2-congenital disorder of glycosylation (ClinVar).

How common is SLC35A2 p.Pro365= (c.1095C>T) in the general population?

SLC35A2 p.Pro365= (c.1095C>T) is very rare (popmax 0.00437%, amr) (gnomAD).

How is SLC35A2-CDG inherited?

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

SLC35A2 p.Pro365=

c.1095C>T · VCV4810766

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00437%, amr)

Conditions

SLC35A2-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.27	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -2.4
Overall
CADD	0.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00437% Admixed American · 2/45,797 alleles

Filtering AF 0.000724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000271%

Overall 0.000661% 8/1,209,641 alleles · very rare exomes 7/1,097,505 · genomes 1/112,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00437%	22,898
East Asian	0.00296%	33,757
South Asian	0.00176%	56,758
European (non-Finnish)	0.000447%	223,711

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: SLC35A2
Protein: p.Pro365=
Coding: c.1095C>T
MANE Select: NM_005660
Type: single nucleotide variant
Location: chrX:48904814 (GRCh38)
Structure: AlphaFold pLDDT 80.59
Residue 365: the 'disordered' region; a UniProt-annotated variant site (in cdg2m); a UniProt-annotated variant site (in cdg2m; reduced udp-galactose transport in patient fibroblasts)

Full SLC35A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SLC35A2-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For SLC35A2-CDG (Orphanet):

Inheritance: Unknown
Onset: Infancy, Neonatal

Similar variants

SLC35A2 p.Gly282Arg Pathogenic ★★ same condition
SLC35A2 p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
SLC35A2 p.Tyr267Cys Likely pathogenic ★★ same condition
SLC35A2 p.Val331Ile Pathogenic ★★ same condition
SLC35A2 p.Ala11Ser Uncertain significance ★★ ⚠ same condition
SLC35A2 p.Ala12Gly Uncertain significance ★★ ⚠ same condition
SLC35A2 p.Ala328Thr Uncertain significance ★★ ⚠ same condition
SLC35A2 p.Ala344Ser 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/slc35a2-p-pro365 (accessed [today's date]).

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