Is SLC19A2 p.Glu66Ter (c.196G>T) pathogenic?

SLC19A2 p.Glu66Ter (c.196G>T) is classified Pathogenic in SLC19A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-04). Very rare (popmax 0.00115%, sas); Associated with sensorineural hearing loss disorder.

What condition is associated with SLC19A2 p.Glu66Ter (c.196G>T)?

SLC19A2 p.Glu66Ter (c.196G>T) is associated with sensorineural hearing loss disorder (ClinVar).

How common is SLC19A2 p.Glu66Ter (c.196G>T) in the general population?

SLC19A2 p.Glu66Ter (c.196G>T) is very rare (popmax 0.00115%, sas) (gnomAD).

SLC19A2 p.Glu66Ter

c.196G>T · rs1658539563 · VCV2202880

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00115%, sas)

Conditions

sensorineural hearing loss 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 1 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -4.2
Overall
CADD	29.5	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 0.00115% South Asian · 1/87,038 alleles

Overall 6.31e-05% 1/1,585,702 alleles · very rare exomes 1/1,433,334 · genomes 0/152,368 · joint denominator

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.Glu66Ter
Coding: c.196G>T
MANE Select: NM_006996
dbSNP: rs1658539563
Type: single nucleotide variant
Location: chr1:169485571 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB

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

Disease context

sensorineural hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC19A2 c.1223+1G>A Pathogenic ★★ same type
SLC19A2 c.807+2T>G Likely pathogenic ★★ same type
SLC19A2 p.Arg162Ter Pathogenic ★★ same type
SLC19A2 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same type
SLC19A2 p.Gln233Ter Pathogenic ★★ same type
SLC19A2 p.Gly105Glu Pathogenic/Likely pathogenic ★★ same type
SLC19A2 p.Gly172Asp Pathogenic/Likely pathogenic ★★ same type
SLC19A2 p.Gly334Asp 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/slc19a2-p-glu66ter (accessed [today's date]).

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