Is SLC35A2 p.Arg34Ser (c.100C>A) pathogenic?

SLC35A2 p.Arg34Ser (c.100C>A) is classified Uncertain significance in SLC35A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely benign (0.2367); Absent from gnomAD v4.1.

How common is SLC35A2 p.Arg34Ser (c.100C>A) in the general population?

SLC35A2 p.Arg34Ser (c.100C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC35A2 p.Arg34Ser (c.100C>A)?

AlphaMissense predicts likely benign (score 0.2367) — an in-silico prediction, not a clinical call.

SLC35A2 p.Arg34Ser

c.100C>A · VCV4532681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2367 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2367	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.91, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 8,120 bp · p 1.6e-17 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Arg34Ser
Coding: c.100C>A
MANE Select: NM_005660
Type: single nucleotide variant
Location: chrX:48909988 (GRCh38)
Structure: AlphaFold pLDDT 80.59

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

Similar variants

SLC35A2 p.Arg34= Likely benign ★★ same residue
SLC35A2 p.Arg34His Uncertain significance ★ ⚠ same residue
SLC35A2 p.Arg34Leu Uncertain significance ★ ⚠ same residue
SLC35A2 p.Gly282Arg Pathogenic ★★ same type
SLC35A2 p.Met1Val Pathogenic/Likely pathogenic ★★ same type
SLC35A2 p.Tyr267Cys Likely pathogenic ★★ same type
SLC35A2 p.Val331Ile Pathogenic ★★ same type
SLC35A2 c.19+1G>C Uncertain significance ★★ same type

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-arg34ser (accessed [today's date]).

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