Is CCDC50 p.Lys226= (c.678A>G) pathogenic?

CCDC50 p.Lys226= (c.678A>G) is classified Benign in CCDC50 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Common (popmax 41.1%, afr) — too common for a highly-penetrant pathogenic allele.

CCDC50 p.Lys226=

Q: How common is CCDC50 p.Lys226= (c.678A>G) in the general population?

CCDC50 p.Lys226= (c.678A>G) is common (popmax 41.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.678A>G · rs2028573 · VCV48157

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 41.1%, afr) — too common for a highly-penetrant pathogenic allele

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 0.043	GERP -4.6
Overall
CADD	0.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 41.1% African / African-American · 30,792/74,902 alleles

Filtering AF 40.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 40.6%

Overall 9.82% 158,388/1,613,458 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	41.1%	2
East Asian	21.2%	5
Admixed American	16.8%	6
Middle Eastern	15%	7
South Asian	11.8%	8
Remaining individualsnot grpmax-eligible	11%	9
Ashkenazi Jewishnot grpmax-eligible	9.4%	11
European (non-Finnish)	7.12%	14
Finnishnot grpmax-eligible	4.24%	24
Amishnot grpmax-eligible	2.74%	36

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.Lys226=
Coding: c.678A>G
MANE Select: NM_178335
dbSNP: rs2028573
Type: single nucleotide variant
Location: chr3:191375291 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90 · 1 PDB
Residue 226: the 'disordered' region

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

Similar variants

CCDC50 p.Ala453Val Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg138Pro Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg227Gln Uncertain significance ★★ same type
CCDC50 p.Arg227Trp Uncertain significance ★★ same type
CCDC50 p.Arg270Ter Uncertain significance ★★ same type
CCDC50 p.Arg274Ter Uncertain significance ★★ same type
CCDC50 p.Arg305Thr Uncertain significance ★★ same type
CCDC50 p.Arg309Gly Uncertain significance ★★ same type

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-lys226 (accessed [today's date]).

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