Is CCDC15 p.Arg915Trp (c.2743C>T) pathogenic?

CCDC15 p.Arg915Trp (c.2743C>T) is classified Uncertain significance in CCDC15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: ambiguous (0.4606); Ultra-rare (popmax 0.0223%, eas).

How common is CCDC15 p.Arg915Trp (c.2743C>T) in the general population?

CCDC15 p.Arg915Trp (c.2743C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about CCDC15 p.Arg915Trp (c.2743C>T)?

AlphaMissense predicts ambiguous (score 0.4606) — an in-silico prediction, not a clinical call.

CCDC15 p.Arg915Trp

c.2743C>T · VCV3263934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4606 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4606	ambiguous
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.67	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 4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 86 kb · p 0.73 · regional, not allelic
Overall
CADD	28.7	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 0.0223% East Asian · 10/44,796 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00958%

Overall 0.0106% 170/1,607,716 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,480
Admixed American	0.0169%	5,928
European (non-Finnish)	0.0118%	8,466
Remaining individualsnot grpmax-eligible	0.00643%	15,559
South Asian	0.00556%	17,977
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,436
African / African-American	0.00134%	74,820

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: CCDC15
Protein: p.Arg915Trp
Coding: c.2743C>T
MANE Select: NM_025004
Type: single nucleotide variant
Location: chr11:125040598 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.02

Full CCDC15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC15 p.Arg181Cys Uncertain significance ★★ ⚠ same type
CCDC15 p.Pro10= Benign ★★ same type
CCDC15 p.Ala110Thr Uncertain significance ★ ⚠ same type
CCDC15 p.Ala140Val Uncertain significance ★ ⚠ same type
CCDC15 p.Ala19Thr Uncertain significance ★ ⚠ same type
CCDC15 p.Ala44Ser Uncertain significance ★ ⚠ same type
CCDC15 p.Ala44Val Uncertain significance ★ ⚠ same type
CCDC15 p.Ala6Thr 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/ccdc15-p-arg915trp (accessed [today's date]).

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