Is CCDC63 p.Thr341Arg (c.1022C>G) pathogenic?

CCDC63 p.Thr341Arg (c.1022C>G) is classified Uncertain significance in CCDC63 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: ambiguous (0.3723); Ultra-rare (popmax 0.0253%, sas).

How common is CCDC63 p.Thr341Arg (c.1022C>G) in the general population?

CCDC63 p.Thr341Arg (c.1022C>G) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about CCDC63 p.Thr341Arg (c.1022C>G)?

AlphaMissense predicts ambiguous (score 0.3723) — an in-silico prediction, not a clinical call.

CCDC63 p.Thr341Arg

c.1022C>G · rs149841694 · VCV2495219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3723	ambiguous
REVEL	0.176	moderately benign-leaning
SaProt	LLR -8.91	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 1.8	GERP -0.35, phastCons 0.93
Regional constraint	o/e 0.92	unconstrained · MANE · 55 kb · p 0.045 · regional, not allelic
Overall
CADD	21.7	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 0.0253% South Asian · 23/91,076 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00143% 23/1,613,966 alleles · ultra-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: CCDC63
Protein: p.Thr341Arg
Coding: c.1022C>G
MANE Select: NM_152591
dbSNP: rs149841694
Type: single nucleotide variant
Location: chr12:110884198 (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.Thr341Met 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.Arg237Cys 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-thr341arg (accessed [today's date]).

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