Is SLC19A2 p.Gly172Asp (c.515G>A) pathogenic?

SLC19A2 p.Gly172Asp (c.515G>A) is classified Pathogenic/Likely pathogenic in SLC19A2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-08). AlphaMissense: likely pathogenic (0.9751); Very rare (popmax 0.00401%, afr); Associated with SLC19A2-related disorder.

What condition is associated with SLC19A2 p.Gly172Asp (c.515G>A)?

SLC19A2 p.Gly172Asp (c.515G>A) is associated with SLC19A2-related disorder, thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Gly172Asp (c.515G>A) in the general population?

SLC19A2 p.Gly172Asp (c.515G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about SLC19A2 p.Gly172Asp (c.515G>A)?

AlphaMissense predicts likely pathogenic (score 0.9751) — an in-silico prediction, not a clinical call.

SLC19A2 p.Gly172Asp

c.515G>A · rs28937595 · VCV5957

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SLC19A2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9751	likely pathogenic ✓ concordant with ClinVar · top 3% in SLC19A2
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.17, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	28.0	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 0.00401% African / African-American · 3/74,906 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000743% 12/1,614,020 alleles · very rare exomes 11/1,461,894 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,969
European (non-Finnish)	0.000763%	131,115

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.Gly172Asp
Coding: c.515G>A
MANE Select: NM_006996
dbSNP: rs28937595
Type: single nucleotide variant
Location: chr1:169477447 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 172: a UniProt-annotated variant site (in trma); an α-helix

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

Disease context

SLC19A2-related disorder

Also linked: thiamine-responsive megaloblastic anemia syndrome

Similar variants

SLC19A2 p.Gly172Val 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.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-p-gly172asp (accessed [today's date]).

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