Is CCDC50 p.Arg76Cys (c.226C>T) pathogenic?

CCDC50 p.Arg76Cys (c.226C>T) is classified Uncertain significance in CCDC50 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-02-14). AlphaMissense: likely benign (0.1593); Very rare (popmax 0.00329%, sas).

How common is CCDC50 p.Arg76Cys (c.226C>T) in the general population?

CCDC50 p.Arg76Cys (c.226C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CCDC50 p.Arg76Cys (c.226C>T)?

AlphaMissense predicts likely benign (score 0.1593) — an in-silico prediction, not a clinical call.

CCDC50 p.Arg76Cys

c.226C>T · rs575240044 · VCV505396

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1593 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1593	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.39 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,052 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00242% 39/1,613,760 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,351
European (non-Finnish)	0.0028%	35,753
African / African-American	0.00267%	37,480
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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.Arg76Cys
Coding: c.226C>T
MANE Select: NM_178335
dbSNP: rs575240044
Type: single nucleotide variant
Location: chr3:191358111 (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.Arg76= Benign ★★ same residue
CCDC50 p.Arg76His Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg76cys (accessed [today's date]).

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