Is SLC19A2 p.Pro60Arg (c.179C>G) pathogenic?

SLC19A2 p.Pro60Arg (c.179C>G) is classified Uncertain significance in SLC19A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-09). AlphaMissense: likely benign (0.0965); Ultra-rare (popmax 0.0283%, afr); Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Pro60Arg (c.179C>G)?

SLC19A2 p.Pro60Arg (c.179C>G) is associated with Inborn genetic diseases, thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Pro60Arg (c.179C>G) in the general population?

SLC19A2 p.Pro60Arg (c.179C>G) is ultra-rare (popmax 0.0283%, afr) (gnomAD).

What do computational predictors say about SLC19A2 p.Pro60Arg (c.179C>G)?

AlphaMissense predicts likely benign (score 0.0965) — an in-silico prediction, not a clinical call.

SLC19A2 p.Pro60Arg

c.179C>G · rs373405573 · VCV501881

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0965 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0965	likely benign
REVEL	0.557	indeterminate
SaProt	LLR -10.48	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.34, phastCons 0.34
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% African / African-American · 21/74,250 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0159%

Overall 0.00385% 61/1,586,172 alleles · ultra-rare exomes 49/1,433,938 · genomes 12/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0283%	3,536
Remaining individualsnot grpmax-eligible	0.0049%	20,418
European (non-Finnish)	0.00309%	32,402
South Asian	0.00115%	87,132

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.Pro60Arg
Coding: c.179C>G
MANE Select: NM_006996
dbSNP: rs373405573
Type: single nucleotide variant
Location: chr1:169485588 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 60: a turn

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

Also linked: thiamine-responsive megaloblastic anemia syndrome

Similar variants

SLC19A2 p.Pro60= Uncertain significance ★ same residue
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

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-pro60arg (accessed [today's date]).

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