Is SLC19A3 p.Glu320Ter (c.958G>T) pathogenic?

SLC19A3 p.Glu320Ter (c.958G>T) is classified Likely pathogenic in SLC19A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). Very rare (popmax 0.00133%, afr).

How common is SLC19A3 p.Glu320Ter (c.958G>T) in the general population?

SLC19A3 p.Glu320Ter (c.958G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

SLC19A3 p.Glu320Ter

c.958G>T · VCV4540820

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 3 of 6
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	39.0	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 0.00133% African / African-American · 1/74,934 alleles

Overall 0.000124% 2/1,613,778 alleles · very rare exomes 1/1,461,550 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,934
European (non-Finnish)	8.47e-05%	1,180,030

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: SLC19A3
Protein: p.Glu320Ter
Coding: c.958G>T
MANE Select: NM_025243
Type: single nucleotide variant
Location: chr2:227698757 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 320: an α-helix

Full SLC19A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC19A3 p.Glu320Ala Uncertain significance ★ ⚠ same residue
SLC19A3 p.Glu320Lys Uncertain significance ★ ⚠ same residue
SLC19A3 p.Glu320Gln Pathogenic same residue
SLC19A3 c.1172+1G>A Pathogenic/Likely pathogenic ★★ same type
SLC19A3 c.1172+2T>G Pathogenic ★★ same type
SLC19A3 c.1173-1G>A Pathogenic/Likely pathogenic ★★ same type
SLC19A3 c.151-1G>C Likely pathogenic ★★ same type
SLC19A3 c.980-14A>G Pathogenic/Likely pathogenic ★★ 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/slc19a3-p-glu320ter (accessed [today's date]).

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