Is CLDN19 p.Pro187= (c.561G>A) pathogenic?

CLDN19 p.Pro187= (c.561G>A) is classified Benign/Likely benign in CLDN19 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Common (popmax 9.84%, afr) — too common for a highly-penetrant pathogenic allele; Associated with renal hypomagnesemia 5 with ocular involvement.

What condition is associated with CLDN19 p.Pro187= (c.561G>A)?

CLDN19 p.Pro187= (c.561G>A) is associated with renal hypomagnesemia 5 with ocular involvement (ClinVar).

CLDN19 p.Pro187=

Q: How common is CLDN19 p.Pro187= (c.561G>A) in the general population?

CLDN19 p.Pro187= (c.561G>A) is common (popmax 9.84%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Primary hypomagnesemia with hypercalciuria and nephrocalcinosis inherited?

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

c.561G>A · rs9660973 · VCV297341

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 9.84%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

renal hypomagnesemia 5 with ocular involvement

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.209	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.9	GERP -3.3
Overall
CADD	2.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.84% African / African-American · 7,320/74,410 alleles

Filtering AF 9.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.57%

Overall 4.34% 68,398/1,577,392 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.84%	10
Amishnot grpmax-eligible	8.44%	12
Middle Eastern	7.31%	14
Ashkenazi Jewishnot grpmax-eligible	6.08%	16
South Asian	5.43%	18
Remaining individualsnot grpmax-eligible	4.63%	22
Admixed American	4.08%	24
European (non-Finnish)	4.08%	25
Finnishnot grpmax-eligible	2.8%	36
East Asian	0.0739%	1,353

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: CLDN19
Protein: p.Pro187=
Coding: c.561G>A
MANE Select: NM_148960
dbSNP: rs9660973
Type: single nucleotide variant
Location: chr1:42735943 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.08

Full CLDN19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal hypomagnesemia 5 with ocular involvement — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary hypomagnesemia with hypercalciuria and nephrocalcinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

CLDN19 p.Pro187Leu Uncertain significance ★★ ⚠ same residue
CLDN19 p.Pro187Ser Uncertain significance ★ ⚠ same residue
CLDN19 p.Gly20Asp Pathogenic/Likely pathogenic ★★ same condition
CLDN19 p.Gly75Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLDN19 p.Leu90Arg Pathogenic/Likely pathogenic ★★ same condition
CLDN19 p.Pro28Leu Likely pathogenic ★★ same condition
CLDN19 c.-150C>T Uncertain significance ★★ same condition
CLDN19 p.Ala216Thr Uncertain significance ★★ ⚠ 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/cldn19-p-pro187 (accessed [today's date]).

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