Is SLC19A1 p.Gly348Arg (c.1042G>A) pathogenic?

SLC19A1 p.Gly348Arg (c.1042G>A) is classified Pathogenic in SLC19A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-21). AlphaMissense: likely pathogenic (0.917); Absent from gnomAD v4.1; Associated with immunodeficiency 114, folate-responsive.

What condition is associated with SLC19A1 p.Gly348Arg (c.1042G>A)?

SLC19A1 p.Gly348Arg (c.1042G>A) is associated with immunodeficiency 114, folate-responsive (ClinVar).

How common is SLC19A1 p.Gly348Arg (c.1042G>A) in the general population?

SLC19A1 p.Gly348Arg (c.1042G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC19A1 p.Gly348Arg (c.1042G>A)?

AlphaMissense predicts likely pathogenic (score 0.917) — an in-silico prediction, not a clinical call.

SLC19A1 p.Gly348Arg

c.1042G>A · rs2077855956 · VCV2663876

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.917 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 114, folate-responsive

Computational evidence

Protein change
AlphaMissense	0.917	likely pathogenic ✓ concordant with ClinVar · top 7% in SLC19A1
REVEL	0.678	pathogenic-leaning
SaProt	LLR -12.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.7, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.89 · regional, not allelic
Overall
CADD	21.5	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: SLC19A1
Protein: p.Gly348Arg
Coding: c.1042G>A
MANE Select: NM_194255
dbSNP: rs2077855956
Type: single nucleotide variant
Location: chr21:45530879 (GRCh38)
Gene constraint: LOEUF 1.585 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.30 · 19 PDB
Residue 348: an α-helix; a UniProt-annotated variant site (in imd114; likely pathogenic; decreased function in positive regulation of cgas/sting signaling pathway and altered activation of immune response; no effect on localization to the cell membrane)

Full SLC19A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 114, folate-responsive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Megaloblastic anemia-immunodeficiency due to folate transporter 1 deficiency (Orphanet):

Onset: Infancy, Neonatal

Similar variants

COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 c.*30G>A Uncertain significance ★★ same type
COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1081Gln Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1183His 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/slc19a1-p-gly348arg (accessed [today's date]).

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