Is SLC35A2 p.Ser356= (c.1068C>T) pathogenic?

SLC35A2 p.Ser356= (c.1068C>T) is classified Benign in SLC35A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Ultra-rare (popmax 0.0458%, sas); Associated with SLC35A2-congenital disorder of glycosylation.

What condition is associated with SLC35A2 p.Ser356= (c.1068C>T)?

SLC35A2 p.Ser356= (c.1068C>T) is associated with SLC35A2-congenital disorder of glycosylation (ClinVar).

How common is SLC35A2 p.Ser356= (c.1068C>T) in the general population?

SLC35A2 p.Ser356= (c.1068C>T) is ultra-rare (popmax 0.0458%, sas) (gnomAD).

How is SLC35A2-CDG inherited?

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

SLC35A2 p.Ser356=

c.1068C>T · rs201330204 · VCV2038309

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, sas)

Conditions

SLC35A2-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.137	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.8	GERP -2.4
Overall
CADD	0.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0458% South Asian · 26/56,751 alleles

Filtering AF 0.0321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.00587% 71/1,209,923 alleles · ultra-rare exomes 64/1,097,660 · genomes 7/112,263 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0458%	2,183
East Asian	0.0148%	6,753
Remaining individualsnot grpmax-eligible	0.0063%	15,867
European (non-Finnish)	0.00402%	24,861
African / African-American	0.00175%	57,285

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.Ser356=
Coding: c.1068C>T
MANE Select: NM_005660
dbSNP: rs201330204
Type: single nucleotide variant
Location: chrX:48904841 (GRCh38)
Structure: AlphaFold pLDDT 80.59
Residue 356: 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-ser356 (accessed [today's date]).

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