Is SLC19A2 c.*60G>A pathogenic?

SLC19A2 c.60G>A is classified Benign in SLC19A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-06-23). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with thiamine-responsive megaloblastic anemia syndrome.

What condition is associated with SLC19A2 c.*60G>A?

SLC19A2 c.*60G>A is associated with thiamine-responsive megaloblastic anemia syndrome (ClinVar).

SLC19A2 c.*60G>A

Q: How common is SLC19A2 c.*60G>A in the general population?

SLC19A2 c.*60G>A is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Thiamine-responsive megaloblastic anemia syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs2678166 · VCV293520

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

thiamine-responsive megaloblastic anemia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -3.7, phastCons 0.006
Non-coding constraint	Z 2.13	1 kb window · o/e 0.84 · regional · uncalibrated
Overall
CADD	6.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,782/44,782 alleles

Filtering AF 99.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.1%

Overall 98.2% 1,563,633/1,591,568 alleles · common exomes 1,413,344/1,439,224 · genomes 150,289/152,344 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
South Asian	99.9%	1
African / African-American	99.7%	1
Admixed American	99.6%	1
Middle Eastern	99.6%	1
Remaining individualsnot grpmax-eligible	98.7%	1
Ashkenazi Jewishnot grpmax-eligible	98.6%	1
Finnishnot grpmax-eligible	97.9%	1
European (non-Finnish)	97.9%	1
Amishnot grpmax-eligible	97.5%	1

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
Coding: c.*60G>A
MANE Select: NM_006996
dbSNP: rs2678166
Type: single nucleotide variant
Location: chr1:169465789 (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

thiamine-responsive megaloblastic anemia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Thiamine-responsive megaloblastic anemia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

SLC19A2 c.1223+1G>A Pathogenic ★★ same condition
SLC19A2 c.807+2T>G Likely pathogenic ★★ same condition
SLC19A2 p.Arg162Ter 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

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-c-star-60g-a (accessed [today's date]).

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