Is CCDC50 p.Ser206Phe (c.617C>T) pathogenic?

CCDC50 p.Ser206Phe (c.617C>T) is classified Conflicting classifications of pathogenicity in CCDC50 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-21). Rare (popmax 0.153%, nfe).

How common is CCDC50 p.Ser206Phe (c.617C>T) in the general population?

CCDC50 p.Ser206Phe (c.617C>T) is rare (popmax 0.153%, nfe) (gnomAD).

CCDC50 p.Ser206Phe

c.617C>T · rs138153104 · VCV228479

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.153%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.135	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 0.25
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.39 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.153% European (non-Finnish) · 1,805/1,179,826 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.121% 1,958/1,613,812 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.768%	130
European (non-Finnish)grpmax	0.153%	654
Remaining individualsnot grpmax-eligible	0.096%	1,041
South Asian	0.0494%	2,024
African / African-American	0.024%	4,167
Admixed American	0.0217%	4,614
Middle Eastern	0.0165%	6,058
Finnishnot grpmax-eligible	0.0109%	9,147
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,796

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser206Phe
Coding: c.617C>T
MANE Select: NM_178335
dbSNP: rs138153104
Type: single nucleotide variant
Location: chr3:191375230 (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.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-ser206phe (accessed [today's date]).

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