Is FXYD2 p.Pro12= (c.36C>G) pathogenic?

FXYD2 p.Pro12= (c.36C>G) is classified Uncertain significance in FXYD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0166%, mid); Associated with renal hypomagnesemia 2.

What condition is associated with FXYD2 p.Pro12= (c.36C>G)?

FXYD2 p.Pro12= (c.36C>G) is associated with renal hypomagnesemia 2 (ClinVar).

How common is FXYD2 p.Pro12= (c.36C>G) in the general population?

FXYD2 p.Pro12= (c.36C>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

FXYD2 p.Pro12=

Q: How is Autosomal dominant primary hypomagnesemia with hypocalciuria inherited?

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

c.36C>G · rs778901593 · VCV880461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

renal hypomagnesemia 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP -0.39, phastCons 1
Overall
CADD	4.887	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,022 alleles

Overall 0.000124% 2/1,610,170 alleles · ultra-rare exomes 2/1,457,964 · genomes 0/152,206 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,022
European (non-Finnish)	8.48e-05%	1,179,126

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: FXYD2
Protein: p.Pro12=
Coding: c.36C>G
MANE Select: NM_001680
dbSNP: rs778901593
Type: single nucleotide variant
Location: chr11:117822707 (GRCh38)

Full FXYD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal hypomagnesemia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant primary hypomagnesemia with hypocalciuria (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

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/fxyd2-p-pro12 (accessed [today's date]).

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