Is CCDC50 p.Thr456= (c.1368T>G) pathogenic?

CCDC50 p.Thr456= (c.1368T>G) is classified Likely benign in CCDC50 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). Very rare (popmax 0.000847%, nfe).

How common is CCDC50 p.Thr456= (c.1368T>G) in the general population?

CCDC50 p.Thr456= (c.1368T>G) is very rare (popmax 0.000847%, nfe) (gnomAD).

CCDC50 p.Thr456=

c.1368T>G · rs1228250972 · VCV2844076

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

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 -0.12	GERP -2.7
Overall
CADD	5.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,179,972 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000684% 10/1,461,816 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.Thr456=
Coding: c.1368T>G
MANE Select: NM_178335
dbSNP: rs1228250972
Type: single nucleotide variant
Location: chr3:191389541 (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

Similar variants

CCDC50 p.Thr456Ser Uncertain significance ★ ⚠ same residue
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

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-thr456 (accessed [today's date]).

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