Is CCDC63 p.Arg237Cys (c.709C>T) pathogenic?

CCDC63 p.Arg237Cys (c.709C>T) is classified Uncertain significance in CCDC63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.2213); Very rare (popmax 0.00223%, eas).

How common is CCDC63 p.Arg237Cys (c.709C>T) in the general population?

CCDC63 p.Arg237Cys (c.709C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CCDC63 p.Arg237Cys (c.709C>T)?

AlphaMissense predicts likely benign (score 0.2213) — an in-silico prediction, not a clinical call.

CCDC63 p.Arg237Cys

c.709C>T · rs775890946 · VCV2230444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2213	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 55 kb · p 0.045 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,840 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000869% 14/1,611,960 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,840
African / African-American	0.00134%	74,800
South Asian	0.0011%	90,886
European (non-Finnish)	0.000933%	107,238

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: CCDC63
Protein: p.Arg237Cys
Coding: c.709C>T
MANE Select: NM_152591
dbSNP: rs775890946
Type: single nucleotide variant
Location: chr12:110881152 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.75

Full CCDC63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC63 p.Arg237His Uncertain significance ★ ⚠ same residue
CCDC63 p.Ala108Thr Uncertain significance ★ ⚠ same type
CCDC63 p.Ala144Val Uncertain significance ★ ⚠ same type
CCDC63 p.Ala27Val Uncertain significance ★ ⚠ same type
CCDC63 p.Ala280Val Uncertain significance ★ ⚠ same type
CCDC63 p.Arg148Trp Uncertain significance ★ ⚠ same type
CCDC63 p.Arg230Gln Uncertain significance ★ ⚠ same type
CCDC63 p.Arg250Gln 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/ccdc63-p-arg237cys (accessed [today's date]).

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