Is SLC19A2 p.Arg162Ter (c.484C>T) pathogenic?

SLC19A2 p.Arg162Ter (c.484C>T) is classified Pathogenic in SLC19A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-02-10). Very rare (popmax 0.0011%, nfe); Associated with SLC19A2-related disorder.

What condition is associated with SLC19A2 p.Arg162Ter (c.484C>T)?

SLC19A2 p.Arg162Ter (c.484C>T) is associated with SLC19A2-related disorder, thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Arg162Ter (c.484C>T) in the general population?

SLC19A2 p.Arg162Ter (c.484C>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

SLC19A2 p.Arg162Ter

c.484C>T · rs74315373 · VCV5955

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

SLC19A2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.36, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,180,014 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000867% 14/1,614,120 alleles · very rare exomes 14/1,461,888 · genomes 0/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0011%	90,770
South Asian	0.0011%	91,068

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: SLC19A2
Protein: p.Arg162Ter
Coding: c.484C>T
MANE Select: NM_006996
dbSNP: rs74315373
Type: single nucleotide variant
Location: chr1:169477478 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 162: an α-helix

Full SLC19A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SLC19A2-related disorder

Also linked: thiamine-responsive megaloblastic anemia syndrome

Similar variants

SLC19A2 c.1223+1G>A Pathogenic ★★ same condition
SLC19A2 c.807+2T>G Likely pathogenic ★★ same condition
SLC19A2 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Gln233Ter Pathogenic ★★ same condition
SLC19A2 p.Gly105Glu Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Gly172Asp Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Gly334Asp Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Ser143Phe Pathogenic ★★ 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/slc19a2-p-arg162ter (accessed [today's date]).

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