Is CCDC3 p.Arg20Cys (c.58C>T) pathogenic?

CCDC3 p.Arg20Cys (c.58C>T) is classified Uncertain significance in CCDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: ambiguous (0.3896); Very rare (popmax 0.00673%, nfe).

How common is CCDC3 p.Arg20Cys (c.58C>T) in the general population?

CCDC3 p.Arg20Cys (c.58C>T) is very rare (popmax 0.00673%, nfe) (gnomAD).

What do computational predictors say about CCDC3 p.Arg20Cys (c.58C>T)?

AlphaMissense predicts ambiguous (score 0.3896) — an in-silico prediction, not a clinical call.

CCDC3 p.Arg20Cys

c.58C>T · VCV3486639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3896	ambiguous
REVEL	0.021	moderately benign-leaning
SaProt	LLR -9.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP 2
Regional constraint	o/e 1.18	unconstrained · MANE · 103 kb · p 0.00074 · regional, not allelic
Overall
CADD	18.43	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 0.00673% European (non-Finnish) · 70/1,040,678 alleles

Filtering AF 0.00542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00497%

Overall 0.00535% 71/1,326,028 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00673%	14,867
Remaining individualsnot grpmax-eligible	0.002%	49,948

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: CCDC3
Protein: p.Arg20Cys
Coding: c.58C>T
MANE Select: NM_031455
Type: single nucleotide variant
Location: chr10:13001513 (GRCh38)
Gene constraint: LOEUF 1.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13

Full CCDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC3 p.Ala19Val Uncertain significance ★ ⚠ same type
CCDC3 p.Ala21Ser Uncertain significance ★ ⚠ same type
CCDC3 p.Ala21Thr Uncertain significance ★ ⚠ same type
CCDC3 p.Ala250Val Uncertain significance ★ ⚠ same type
CCDC3 p.Ala253Thr Uncertain significance ★ ⚠ same type
CCDC3 p.Arg213Cys Uncertain significance ★ ⚠ same type
CCDC3 p.Arg215Trp Uncertain significance ★ ⚠ same type
CCDC3 p.Arg218Pro 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/ccdc3-p-arg20cys (accessed [today's date]).

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