Is SLC35A2 p.Pro341Ser (c.1021C>T) pathogenic?

SLC35A2 p.Pro341Ser (c.1021C>T) is classified Uncertain significance in SLC35A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: ambiguous (0.5073); Absent from gnomAD v4.1; Associated with SLC35A2-congenital disorder of glycosylation.

What condition is associated with SLC35A2 p.Pro341Ser (c.1021C>T)?

SLC35A2 p.Pro341Ser (c.1021C>T) is associated with SLC35A2-congenital disorder of glycosylation (ClinVar).

How common is SLC35A2 p.Pro341Ser (c.1021C>T) in the general population?

SLC35A2 p.Pro341Ser (c.1021C>T) is absent from gnomAD v4.1 (gnomAD).

How is SLC35A2-CDG inherited?

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

What do computational predictors say about SLC35A2 p.Pro341Ser (c.1021C>T)?

AlphaMissense predicts ambiguous (score 0.5073) — an in-silico prediction, not a clinical call.

SLC35A2 p.Pro341Ser

c.1021C>T · rs782526017 · VCV2098625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5073 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

SLC35A2-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.5073	ambiguous
REVEL	0.385	indeterminate
SaProt	LLR -13.35	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 8,120 bp · p 1.6e-17 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC35A2
Protein: p.Pro341Ser
Coding: c.1021C>T
MANE Select: NM_005660
dbSNP: rs782526017
Type: single nucleotide variant
Location: chrX:48904888 (GRCh38)
Structure: AlphaFold pLDDT 80.59
Residue 341: 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-pro341ser (accessed [today's date]).

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