Is CCDC50 p.Gln268Ter (c.802C>T) pathogenic?

CCDC50 p.Gln268Ter (c.802C>T) is classified Likely pathogenic in CCDC50 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). Very rare (popmax 8.48e-05%, nfe); Associated with autosomal dominant nonsyndromic hearing loss 44.

What condition is associated with CCDC50 p.Gln268Ter (c.802C>T)?

CCDC50 p.Gln268Ter (c.802C>T) is associated with autosomal dominant nonsyndromic hearing loss 44 (ClinVar).

How common is CCDC50 p.Gln268Ter (c.802C>T) in the general population?

CCDC50 p.Gln268Ter (c.802C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CCDC50 p.Gln268Ter

c.802C>T · VCV3572930

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

autosomal dominant nonsyndromic hearing loss 44

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.88, phastCons 0.004
Overall
CADD	35.0	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 8.48e-05% European (non-Finnish) · 1/1,179,852 alleles

Overall 6.84e-05% 1/1,461,562 alleles · very rare

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
Protein: p.Gln268Ter
Coding: c.802C>T
MANE Select: NM_178335
Type: single nucleotide variant
Location: chr3:191375415 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90 · 1 PDB
Residue 268: the 'disordered' region

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.Gln268= Likely benign ★ same residue
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 c.976+6A>G Benign ★★ same condition
CCDC50 p.Asp295Tyr 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-p-gln268ter (accessed [today's date]).

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