Is BDP1 p.Pro2358= (c.7074G>T) pathogenic?

BDP1 p.Pro2358= (c.7074G>T) is classified Benign in BDP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-07-14). Common (popmax 55.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with hearing loss, autosomal recessive 112.

What condition is associated with BDP1 p.Pro2358= (c.7074G>T)?

BDP1 p.Pro2358= (c.7074G>T) is associated with hearing loss, autosomal recessive 112 (ClinVar).

BDP1 p.Pro2358=

Q: How common is BDP1 p.Pro2358= (c.7074G>T) in the general population?

BDP1 p.Pro2358= (c.7074G>T) is common (popmax 55.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7074G>T · rs469039 · VCV508090

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 55.1%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

hearing loss, autosomal recessive 112

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.018	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP 0.48
Overall
CADD	3.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 55.1% South Asian · 50,119/91,002 alleles

Filtering AF 54.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 54.5%

Overall 47.8% 770,170/1,612,150 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	64.3%	2
South Asiangrpmax	55.1%	2
Finnishnot grpmax-eligible	52.8%	2
European (non-Finnish)	48.8%	2
Middle Eastern	48.8%	2
Ashkenazi Jewishnot grpmax-eligible	48.3%	2
Remaining individualsnot grpmax-eligible	47.6%	2
African / African-American	37.9%	3
East Asian	37.2%	3
Admixed American	31%	3

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BDP1
Protein: p.Pro2358=
Coding: c.7074G>T
MANE Select: NM_018429
dbSNP: rs469039
Type: single nucleotide variant
Location: chr5:71553194 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 37.23 · 13 PDB

Full BDP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hearing loss, autosomal recessive 112 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BDP1 p.Pro2358Leu Uncertain significance ★ ⚠ same residue
BDP1 p.Arg935Ile Uncertain significance ★★ ⚠ same condition
BDP1 c.2373-15C>T Benign/Likely benign ★★ same condition
BDP1 c.4060-77G>A Benign ★★ same condition
BDP1 c.5893-36G>A Benign ★★ same condition
BDP1 p.Asp38Glu Benign ★★ same condition
BDP1 p.Gly1180Ser Benign ★★ same condition
BDP1 p.Ile1264Met Benign ★★ 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/bdp1-p-pro2358 (accessed [today's date]).

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