Is CCDC17 p.Arg406Trp (c.1216C>T) pathogenic?

CCDC17 p.Arg406Trp (c.1216C>T) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). AlphaMissense: likely benign (0.0974); Ultra-rare (popmax 0.033%, mid).

How common is CCDC17 p.Arg406Trp (c.1216C>T) in the general population?

CCDC17 p.Arg406Trp (c.1216C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CCDC17 p.Arg406Trp (c.1216C>T)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

CCDC17 p.Arg406Trp

c.1216C>T · VCV3828396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.32	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 -0.17	GERP -1.9
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	22.8	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 0.033% Middle Eastern · 2/6,068 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00182% 29/1,593,774 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,034
Ashkenazi Jewishnot grpmax-eligible	0.00687%	14,559
African / African-American	0.00403%	24,785
Remaining individualsnot grpmax-eligible	0.00324%	30,911
South Asian	0.00228%	43,835
European (non-Finnish)	0.00154%	65,034

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.Arg406Trp
Coding: c.1216C>T
MANE Select: NM_001114938
Type: single nucleotide variant
Location: chr1:45621453 (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.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
CCDC17 p.Ala433Val 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-arg406trp (accessed [today's date]).

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