Is CCDC17 p.Arg504Trp (c.1510C>T) pathogenic?

CCDC17 p.Arg504Trp (c.1510C>T) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1933); Ultra-rare (popmax 0.0173%, afr).

How common is CCDC17 p.Arg504Trp (c.1510C>T) in the general population?

CCDC17 p.Arg504Trp (c.1510C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about CCDC17 p.Arg504Trp (c.1510C>T)?

AlphaMissense predicts likely benign (score 0.1933) — an in-silico prediction, not a clinical call.

CCDC17 p.Arg504Trp

c.1510C>T · rs374329461 · VCV2403880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1933	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -4.76	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 2.8	GERP -0.87, phastCons 0.79
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	24.1	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 0.0173% African / African-American · 13/75,034 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00682% 110/1,613,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,772
East Asian	0.0134%	7,480
European (non-Finnish)	0.00746%	13,407
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,476
South Asian	0.0011%	91,036

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: CCDC17
Protein: p.Arg504Trp
Coding: c.1510C>T
MANE Select: NM_001114938
dbSNP: rs374329461
Type: single nucleotide variant
Location: chr1:45620992 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.58

Full CCDC17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC17 p.Arg504Gln Uncertain significance ★ ⚠ same residue
CCDC17 p.Arg504Pro Uncertain significance ★ ⚠ same residue
CCDC17 p.Ala146Thr Uncertain significance ★ ⚠ same type
CCDC17 p.Ala146Val Uncertain significance ★ ⚠ same type
CCDC17 p.Ala154Thr Uncertain significance ★ ⚠ same type
CCDC17 p.Ala195Ser Uncertain significance ★ ⚠ same type
CCDC17 p.Ala197Val Uncertain significance ★ ⚠ same type
CCDC17 p.Ala289Gly 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/ccdc17-p-arg504trp (accessed [today's date]).

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