Is SCNN1B p.Phe293= (c.879C>T) pathogenic?

SCNN1B p.Phe293= (c.879C>T) is classified Benign/Likely benign in SCNN1B (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-27). Common (popmax 22.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Liddle syndrome 1.

How is Liddle syndrome inherited?

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

SCNN1B p.Phe293=

Q: What condition is associated with SCNN1B p.Phe293= (c.879C>T)?

SCNN1B p.Phe293= (c.879C>T) is associated with Liddle syndrome 1, bronchiectasis with or without elevated sweat chloride 1, pseudohypoaldosteronism, type IB1, autosomal recessive (ClinVar).

Q: How common is SCNN1B p.Phe293= (c.879C>T) in the general population?

SCNN1B p.Phe293= (c.879C>T) is common (popmax 22.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.879C>T · rs250563 · VCV178802

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 22.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Liddle syndrome 1

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 -7	GERP -4
Overall
CADD	1.337	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.4% African / African-American · 16,787/74,852 alleles

Filtering AF 22.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 22%

Overall 5.46% 88,015/1,610,998 alleles · common exomes 73,153/1,458,784 · genomes 14,862/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.4%	4
Finnishnot grpmax-eligible	8.53%	12
Middle Eastern	7.64%	13
Remaining individualsnot grpmax-eligible	5.61%	18
Ashkenazi Jewishnot grpmax-eligible	4.87%	21
European (non-Finnish)	4.78%	21
Admixed American	4.42%	23
Amishnot grpmax-eligible	1.98%	51
South Asian	1.55%	65
East Asian	0.0223%	4,488

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: SCNN1B
Protein: p.Phe293=
Coding: c.879C>T
MANE Select: NM_000336
dbSNP: rs250563
Type: single nucleotide variant
Location: chr16:23367958 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.96 · 5 PDB
Residue 293: an α-helix

Full SCNN1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Liddle syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: bronchiectasis with or without elevated sweat chloride 1 pseudohypoaldosteronism, type IB1, autosomal recessive

For Liddle syndrome (Orphanet):

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

Similar variants

SCNN1B p.Phe293Tyr Uncertain significance ★ ⚠ same residue
SCNN1B p.Arg566Ter Pathogenic ★★ same condition
SCNN1B p.Pro616Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
SCNN1B p.Pro617Ser Pathogenic/Likely pathogenic ★★ same condition
SCNN1B p.Pro618Ser Pathogenic/Likely pathogenic ★★ same condition
SCNN1B c.1270+6C>T Uncertain significance ★★ same condition
SCNN1B p.Ala336Thr Uncertain significance ★★ ⚠ same condition
SCNN1B p.Ala435Val 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/scnn1b-p-phe293 (accessed [today's date]).

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