Is CCDC50 c.976+6A>G pathogenic?

CCDC50 c.976+6A>G is classified Benign in CCDC50 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 68.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 44.

What condition is associated with CCDC50 c.976+6A>G?

CCDC50 c.976+6A>G is associated with autosomal dominant nonsyndromic hearing loss 44 (ClinVar).

CCDC50 c.976+6A>G

Q: How common is CCDC50 c.976+6A>G in the general population?

CCDC50 c.976+6A>G is common (popmax 68.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs4677729 · VCV48160

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 68.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal dominant nonsyndromic hearing loss 44

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +6	donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -4.8, phastCons 0.001
Non-coding constraint	Z 2.51	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	1.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.3% African / African-American · 51,072/74,766 alleles

Filtering AF 67.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.6%

Overall 40.8% 657,195/1,610,156 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	68.3%	1
Admixed American	48.8%	2
Ashkenazi Jewishnot grpmax-eligible	45.9%	2
Remaining individualsnot grpmax-eligible	41.5%	2
East Asian	41.5%	2
European (non-Finnish)	39.1%	3
Middle Eastern	39.1%	3
Finnishnot grpmax-eligible	36.9%	3
South Asian	35.9%	3
Amishnot grpmax-eligible	25.8%	4

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: CCDC50
Coding: c.976+6A>G
MANE Select: NM_178335
dbSNP: rs4677729
Type: single nucleotide variant
Location: chr3:191375595 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90 · 1 PDB

Full CCDC50 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 44 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCDC50 p.Arg227Trp Uncertain significance ★★ same condition
CCDC50 c.1092+58C>T Benign ★★ same condition
CCDC50 c.1242+10G>A Benign ★★ same condition
CCDC50 c.50-4C>G Benign ★★ same condition
CCDC50 c.976+56A>G Benign ★★ same condition
CCDC50 p.Asp295Tyr Benign ★★ same condition
CCDC50 p.His217= Benign ★★ same condition
CCDC50 p.Ile258Asn 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/ccdc50-c-976-plus-6a-g (accessed [today's date]).

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