Is CCDC93 p.Arg456Trp (c.1366C>T) pathogenic?

CCDC93 p.Arg456Trp (c.1366C>T) is classified Uncertain significance in CCDC93 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely benign (0.1529); Ultra-rare (popmax 0.0248%, eas).

How common is CCDC93 p.Arg456Trp (c.1366C>T) in the general population?

CCDC93 p.Arg456Trp (c.1366C>T) is ultra-rare (popmax 0.0248%, eas) (gnomAD).

What do computational predictors say about CCDC93 p.Arg456Trp (c.1366C>T)?

AlphaMissense predicts likely benign (score 0.1529) — an in-silico prediction, not a clinical call.

CCDC93 p.Arg456Trp

c.1366C>T · rs142085524 · VCV3139644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0248%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1529	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -12.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.24, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 94 kb · p 0.0042 · regional, not allelic
Overall
CADD	28.5	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 0.0248% East Asian · 11/44,420 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00119% 19/1,597,720 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0248%	4,038
Finnishnot grpmax-eligible	0.00314%	31,856
African / African-American	0.00269%	37,157
Remaining individualsnot grpmax-eligible	0.00161%	61,922
South Asian	0.00116%	86,320
European (non-Finnish)	0.00017%	586,999

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: CCDC93
Protein: p.Arg456Trp
Coding: c.1366C>T
MANE Select: NM_019044
dbSNP: rs142085524
Type: single nucleotide variant
Location: chr2:117944071 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.49 · 4 PDB
Residue 456: the 'sufficient for interaction with washc2c' region

Full CCDC93 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC93 p.Arg456Gln Uncertain significance ★ ⚠ same residue
CCDC93 p.Pro228Leu Benign ★★ same type
CCDC93 p.Ala226Val Uncertain significance ★ ⚠ same type
CCDC93 p.Ala262Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala272Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala370Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala510Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala628Val 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/ccdc93-p-arg456trp (accessed [today's date]).

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