Is SLC19A2 p.Ala183Val (c.548C>T) pathogenic?

SLC19A2 p.Ala183Val (c.548C>T) is classified Uncertain significance in SLC19A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.1016); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Ala183Val (c.548C>T)?

SLC19A2 p.Ala183Val (c.548C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SLC19A2 p.Ala183Val (c.548C>T) in the general population?

SLC19A2 p.Ala183Val (c.548C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about SLC19A2 p.Ala183Val (c.548C>T)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

SLC19A2 p.Ala183Val

c.548C>T · VCV3442961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -7.80	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 2.6	GERP -0.61, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	18.26	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 0.000169% European (non-Finnish) · 2/1,180,054 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,068 alleles · very rare exomes 0/1,461,890 · genomes 2/152,178 · 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.Ala183Val
Coding: c.548C>T
MANE Select: NM_006996
Type: single nucleotide variant
Location: chr1:169477414 (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

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

Similar variants

SLC19A2 p.Ala201Gly Uncertain significance ★★ ⚠ same condition
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SLC19A2 p.Arg275Cys Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Glu321Lys Uncertain significance ★★ same condition
SLC19A2 p.Gly184Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly235Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly362Glu Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly447Ser 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/slc19a2-p-ala183val (accessed [today's date]).

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