Is SLC11A2 p.Pro5= (c.15T>C) pathogenic?

SLC11A2 p.Pro5= (c.15T>C) is classified Uncertain significance in SLC11A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.112%, amr); Associated with microcytic anemia with liver iron overload.

What condition is associated with SLC11A2 p.Pro5= (c.15T>C)?

SLC11A2 p.Pro5= (c.15T>C) is associated with microcytic anemia with liver iron overload (ClinVar).

How common is SLC11A2 p.Pro5= (c.15T>C) in the general population?

SLC11A2 p.Pro5= (c.15T>C) is rare (popmax 0.112%, amr) (gnomAD).

How is Microcytic anemia with liver iron overload inherited?

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

SLC11A2 p.Pro5=

c.15T>C · rs192462172 · VCV881288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.112%, amr)

Conditions

microcytic anemia with liver iron overload

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 1.3	GERP -0.96, phastCons 0.18
Overall
CADD	8.755	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% Admixed American · 67/59,990 alleles

Filtering AF 0.0902% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0824%

Overall 0.0322% 516/1,600,638 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.112%	895
European (non-Finnish)	0.0364%	2,747
Remaining individualsnot grpmax-eligible	0.0322%	3,101
African / African-American	0.00534%	18,722

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: SLC11A2
Protein: p.Pro5=
Coding: c.15T>C
MANE Select: NM_000617
dbSNP: rs192462172
Type: single nucleotide variant
Location: chr12:51010714 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.83 · 7 PDB
Residue 5: the 'disordered' region

Full SLC11A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcytic anemia with liver iron overload — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Microcytic anemia with liver iron overload (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SLC11A2 p.Ala555Thr Uncertain significance ★★ same condition
SLC11A2 p.Asn311Ser Uncertain significance ★★ ⚠ same condition
SLC11A2 p.Ser350Leu Uncertain significance ★★ ⚠ same condition
SLC11A2 p.Ser66Asn Uncertain significance ★★ ⚠ same condition
SLC11A2 c.1348-10T>C Benign/Likely benign ★★ same condition
SLC11A2 c.1576-14A>G Benign/Likely benign ★★ same condition
SLC11A2 c.309+44A>C Benign ★★ same condition
SLC11A2 c.34+11G>A Benign/Likely benign ★★ 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/slc11a2-p-pro5 (accessed [today's date]).

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