Is BSND p.Met1Ile (c.3G>A) pathogenic?

BSND p.Met1Ile (c.3G>A) is classified Pathogenic/Likely pathogenic in BSND (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0145%, nfe); Associated with BSND-related disorder.

What condition is associated with BSND p.Met1Ile (c.3G>A)?

BSND p.Met1Ile (c.3G>A) is associated with BSND-related disorder, Bartter disease type 4A, Bartter syndrome (ClinVar).

How common is BSND p.Met1Ile (c.3G>A) in the general population?

BSND p.Met1Ile (c.3G>A) is ultra-rare (popmax 0.0145%, nfe) (gnomAD).

BSND p.Met1Ile

c.3G>A · rs74315286 · VCV4384

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, nfe)

Conditions

BSND-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.902	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0145% European (non-Finnish) · 171/1,180,036 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.011% 177/1,613,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0145%	6,901
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00267%	37,470

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: BSND
Protein: p.Met1Ile
Coding: c.3G>A
MANE Select: NM_057176
dbSNP: rs74315286
Type: single nucleotide variant
Location: chr1:54999189 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 1: the 'regulates channel membrane trafficking and ion conductance' region

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

Disease context

BSND-related disorder

Also linked: Bartter disease type 4A Bartter syndrome

Similar variants

BSND p.Met1Leu Pathogenic ★★ same residue
BSND c.178-2A>C Likely pathogenic ★★ same condition
BSND c.272+1G>T Pathogenic/Likely pathogenic ★★ same condition
BSND p.Arg8Trp Pathogenic/Likely pathogenic ★★ same condition
BSND p.Gln95Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Glu148Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Glu4Ter Pathogenic ★★ same condition
BSND p.Glu88Ter Pathogenic/Likely 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/bsnd-p-met1ile (accessed [today's date]).

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