Is SLC35A2 p.Arg166= (c.498G>A) pathogenic?

SLC35A2 p.Arg166= (c.498G>A) is classified Likely benign in SLC35A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). No allele count reported in gnomAD v4.1 (AN 1,192,159); Associated with SLC35A2-congenital disorder of glycosylation.

What condition is associated with SLC35A2 p.Arg166= (c.498G>A)?

SLC35A2 p.Arg166= (c.498G>A) is associated with SLC35A2-congenital disorder of glycosylation (ClinVar).

How common is SLC35A2 p.Arg166= (c.498G>A) in the general population?

SLC35A2 p.Arg166= (c.498G>A) is no allele count reported in gnomAD v4.1 (AN 1,192,159) (gnomAD).

How is SLC35A2-CDG inherited?

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

SLC35A2 p.Arg166=

c.498G>A · VCV3681703

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,192,159)

Conditions

SLC35A2-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.7	GERP 0.24, phastCons 1
Overall
CADD	14.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,192,159). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SLC35A2
Protein: p.Arg166=
Coding: c.498G>A
MANE Select: NM_005660
Type: single nucleotide variant
Location: chrX:48905411 (GRCh38)
Structure: AlphaFold pLDDT 80.59
Residue 166: a UniProt-annotated variant site (in cdg2m)

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.Arg166Gln Uncertain significance ★★ ⚠ same residue
SLC35A2 p.Arg166Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-arg166 (accessed [today's date]).

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