Is CCDC17 p.Arg542Trp (c.1624C>T) pathogenic?

CCDC17 p.Arg542Trp (c.1624C>T) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: ambiguous (0.4831); Ultra-rare (popmax 0.0329%, nfe).

How common is CCDC17 p.Arg542Trp (c.1624C>T) in the general population?

CCDC17 p.Arg542Trp (c.1624C>T) is ultra-rare (popmax 0.0329%, nfe) (gnomAD).

What do computational predictors say about CCDC17 p.Arg542Trp (c.1624C>T)?

AlphaMissense predicts ambiguous (score 0.4831) — an in-silico prediction, not a clinical call.

CCDC17 p.Arg542Trp

c.1624C>T · rs764795876 · VCV2369865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4831 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4831	ambiguous
REVEL	0.449	indeterminate
SaProt	LLR -14.43	damaging
Splicing
SpliceAI	Δ0.25	acceptor loss, 20 bp away · masked 0 · deltas
Pangolin	Δ0.27	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.7	GERP -1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	25.9	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 0.0329% European (non-Finnish) · 388/1,178,572 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.0263% 424/1,610,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0329%	3,038
Remaining individualsnot grpmax-eligible	0.0176%	5,675
African / African-American	0.0173%	5,771
Middle Eastern	0.0165%	6,060
Finnishnot grpmax-eligible	0.011%	9,121
Admixed American	0.00505%	19,803
East Asian	0.00223%	44,808

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.Arg542Trp
Coding: c.1624C>T
MANE Select: NM_001114938
dbSNP: rs764795876
Type: single nucleotide variant
Location: chr1:45620809 (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.Arg542Gln 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
CCDC17 p.Ala410Asp 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-arg542trp (accessed [today's date]).

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