Is CCDC17 p.Leu166Pro (c.497T>C) pathogenic?

CCDC17 p.Leu166Pro (c.497T>C) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: ambiguous (0.5007); Ultra-rare (popmax 0.0168%, mid).

How common is CCDC17 p.Leu166Pro (c.497T>C) in the general population?

CCDC17 p.Leu166Pro (c.497T>C) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

What do computational predictors say about CCDC17 p.Leu166Pro (c.497T>C)?

AlphaMissense predicts ambiguous (score 0.5007) — an in-silico prediction, not a clinical call.

CCDC17 p.Leu166Pro

c.497T>C · VCV3486381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5007 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5007	ambiguous · top 10% in CCDC17
REVEL	0.181	moderately benign-leaning
SaProt	LLR -14.21	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 1.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	24.3	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 0.0168% Middle Eastern · 1/5,946 alleles

Filtering AF 0.00289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00258%

Overall 0.0032% 50/1,561,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,946
Remaining individualsnot grpmax-eligible	0.00831%	12,038
European (non-Finnish)	0.00382%	26,201

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.Leu166Pro
Coding: c.497T>C
MANE Select: NM_001114938
Type: single nucleotide variant
Location: chr1:45623114 (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-leu166pro (accessed [today's date]).

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