Is SLC12A2 p.Pro802Ser (c.2404C>T) pathogenic?

SLC12A2 p.Pro802Ser (c.2404C>T) is classified Uncertain significance in SLC12A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely pathogenic (0.6992); Very rare (popmax 0.000372%); Associated with Inborn genetic diseases.

What condition is associated with SLC12A2 p.Pro802Ser (c.2404C>T)?

SLC12A2 p.Pro802Ser (c.2404C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SLC12A2 p.Pro802Ser (c.2404C>T) in the general population?

SLC12A2 p.Pro802Ser (c.2404C>T) is very rare (popmax 0.000372%) (gnomAD).

What do computational predictors say about SLC12A2 p.Pro802Ser (c.2404C>T)?

AlphaMissense predicts likely pathogenic (score 0.6992) — an in-silico prediction, not a clinical call.

SLC12A2 p.Pro802Ser

c.2404C>T · rs778376847 · VCV3162823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000372%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6992	likely pathogenic
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.7, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 23 kb · p 8.9e-12 · regional, not allelic
Overall
CADD	27.3	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 0.000372%

Overall 0.000372% 6/1,613,584 alleles · very rare exomes 0/1,461,448 · genomes 6/152,136 · joint denominator

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: SLC12A2
Protein: p.Pro802Ser
Coding: c.2404C>T
MANE Select: NM_001046
dbSNP: rs778376847
Type: single nucleotide variant
Location: chr5:128158093 (GRCh38)
Gene constraint: LOEUF 0.721 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.23 · 14 PDB
Residue 802: an α-helix

Full SLC12A2 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

Similar variants

SLC12A2 p.Pro802Ala Uncertain significance ★ ⚠ same residue
SLC12A2 p.Ala106Glu Uncertain significance ★★ ⚠ same condition
SLC12A2 p.Ala147Thr Uncertain significance ★★ ⚠ same condition
SLC12A2 p.Ala377Thr Uncertain significance ★★ ⚠ same condition
SLC12A2 p.Arg1148Gln Uncertain significance ★★ ⚠ same condition
SLC12A2 p.Asn474Ile Uncertain significance ★★ ⚠ same condition
SLC12A2 p.Asn551Lys Uncertain significance ★★ ⚠ same condition
SLC12A2 p.Asp119Gly 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/slc12a2-p-pro802ser (accessed [today's date]).

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