Is CCDC63 p.Ala280Val (c.839C>T) pathogenic?

CCDC63 p.Ala280Val (c.839C>T) is classified Uncertain significance in CCDC63 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely benign (0.1133); Ultra-rare (popmax 0.0507%, afr).

How common is CCDC63 p.Ala280Val (c.839C>T) in the general population?

CCDC63 p.Ala280Val (c.839C>T) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

What do computational predictors say about CCDC63 p.Ala280Val (c.839C>T)?

AlphaMissense predicts likely benign (score 0.1133) — an in-silico prediction, not a clinical call.

CCDC63 p.Ala280Val

c.839C>T · VCV3486807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1133 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1133	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.98	GERP 0.97, phastCons 0.98
Regional constraint	o/e 0.92	unconstrained · MANE · 55 kb · p 0.045 · regional, not allelic
Overall
CADD	22.7	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 0.0507% African / African-American · 38/74,896 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.00583% 94/1,613,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,971
Admixed American	0.00668%	14,969
European (non-Finnish)	0.00424%	23,593
Remaining individualsnot grpmax-eligible	0.0032%	31,226

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.Ala280Val
Coding: c.839C>T
MANE Select: NM_152591
Type: single nucleotide variant
Location: chr12:110881282 (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.Ala108Thr Uncertain significance ★ ⚠ same type
CCDC63 p.Ala144Val Uncertain significance ★ ⚠ same type
CCDC63 p.Ala27Val 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
CCDC63 p.Arg237His 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-ala280val (accessed [today's date]).

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