Is CCDC50 p.Ser423= (c.1269C>A) pathogenic?

CCDC50 p.Ser423= (c.1269C>A) is classified Benign in CCDC50 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 80.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 44.

What condition is associated with CCDC50 p.Ser423= (c.1269C>A)?

CCDC50 p.Ser423= (c.1269C>A) is associated with autosomal dominant nonsyndromic hearing loss 44 (ClinVar).

CCDC50 p.Ser423=

Q: How common is CCDC50 p.Ser423= (c.1269C>A) in the general population?

CCDC50 p.Ser423= (c.1269C>A) is common (popmax 80.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1269C>A · rs364519 · VCV48151

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 80.9%, 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -3.5, phastCons 0.37
Overall
CADD	3.661	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 80.9% African / African-American · 60,597/74,866 alleles

Filtering AF 80.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 80.2%

Overall 48.9% 787,340/1,608,742 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	80.9%	1
East Asian	64.7%	2
Admixed American	60.5%	2
South Asian	51.8%	2
Ashkenazi Jewishnot grpmax-eligible	50.4%	2
Remaining individualsnot grpmax-eligible	50%	2
Middle Eastern	47.2%	2
European (non-Finnish)	45.7%	2
Finnishnot grpmax-eligible	44.4%	2
Amishnot grpmax-eligible	34.3%	3

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.Ser423=
Coding: c.1269C>A
MANE Select: NM_178335
dbSNP: rs364519
Type: single nucleotide variant
Location: chr3:191382772 (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 c.976+6A>G Benign ★★ same condition
CCDC50 p.Asp295Tyr Benign ★★ same condition
CCDC50 p.His217= 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-ser423 (accessed [today's date]).

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