Is SCNN1A p.Pro113= (c.339C>G) pathogenic?

SCNN1A p.Pro113= (c.339C>G) is classified Uncertain significance in SCNN1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-09). Very rare (popmax 0.00267%, afr); Associated with Liddle syndrome 3.

How common is SCNN1A p.Pro113= (c.339C>G) in the general population?

SCNN1A p.Pro113= (c.339C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Liddle syndrome inherited?

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

SCNN1A p.Pro113=

Q: What condition is associated with SCNN1A p.Pro113= (c.339C>G)?

SCNN1A p.Pro113= (c.339C>G) is associated with Liddle syndrome 3, pseudohypoaldosteronism, type IB1, autosomal recessive, bronchiectasis with or without elevated sweat chloride 2 (ClinVar).

c.339C>G · VCV3575144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Liddle syndrome 3

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 -9	GERP -4.9
Overall
CADD	0.612	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,106 alleles · very rare exomes 1/1,461,884 · genomes 1/152,222 · 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: SCNN1A
Protein: p.Pro113=
Coding: c.339C>G
MANE Select: NM_001038
Type: single nucleotide variant
Location: chr12:6374445 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.66 · 3 PDB

Full SCNN1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Liddle syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudohypoaldosteronism, type IB1, autosomal recessive bronchiectasis with or without elevated sweat chloride 2

For Liddle syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

SCNN1A p.Pro113Ala Uncertain significance ★ same residue
SCNN1A c.1360+2T>G Pathogenic ★★ same condition
SCNN1A c.1439+1G>A Pathogenic/Likely pathogenic ★★ same condition
SCNN1A c.685-1G>A Likely pathogenic ★★ same condition
SCNN1A c.875+1G>A Pathogenic/Likely pathogenic ★★ same condition
SCNN1A p.Arg492Ter Pathogenic ★★ same condition
SCNN1A p.Arg508Ter Pathogenic/Likely pathogenic ★★ same condition
SCNN1A p.Arg56Ter 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/scnn1a-p-pro113 (accessed [today's date]).

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