Is SLC19A3 p.Lys194Asn (c.582G>T) pathogenic?

SLC19A3 p.Lys194Asn (c.582G>T) is classified Uncertain significance in SLC19A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.2554); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SLC19A3 p.Lys194Asn (c.582G>T)?

SLC19A3 p.Lys194Asn (c.582G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SLC19A3 p.Lys194Asn (c.582G>T) in the general population?

SLC19A3 p.Lys194Asn (c.582G>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about SLC19A3 p.Lys194Asn (c.582G>T)?

AlphaMissense predicts likely benign (score 0.2554) — an in-silico prediction, not a clinical call.

SLC19A3 p.Lys194Asn

c.582G>T · rs754828557 · VCV2274669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2554 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2554	likely benign
REVEL	0.383	indeterminate
SaProt	LLR -4.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.99	GERP -0.37, phastCons 0.97
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.85 · 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

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,052 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,024 alleles · very rare exomes 6/1,461,890 · genomes 2/152,134 · 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: SLC19A3
Protein: p.Lys194Asn
Coding: c.582G>T
MANE Select: NM_025243
dbSNP: rs754828557
Type: single nucleotide variant
Location: chr2:227699133 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC19A3 p.Lys194= Likely benign ★ same residue
SLC19A3 p.Ala288Thr Uncertain significance ★★ ⚠ same condition
SLC19A3 p.Ala307Pro Uncertain significance ★★ same condition
SLC19A3 p.Asn340Ser Uncertain significance ★★ ⚠ same condition
SLC19A3 p.Gly154Glu Uncertain significance ★★ ⚠ same condition
SLC19A3 p.Leu177Ser Uncertain significance ★★ ⚠ same condition
SLC19A3 p.Leu73Phe Uncertain significance ★★ ⚠ same condition
SLC19A3 p.Met421Leu Uncertain significance ★★ ⚠ 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/slc19a3-p-lys194asn (accessed [today's date]).

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