Is CCDC17 p.Ala195Ser (c.583G>T) pathogenic?

CCDC17 p.Ala195Ser (c.583G>T) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0972); Absent from gnomAD v4.1.

How common is CCDC17 p.Ala195Ser (c.583G>T) in the general population?

CCDC17 p.Ala195Ser (c.583G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC17 p.Ala195Ser (c.583G>T)?

AlphaMissense predicts likely benign (score 0.0972) — an in-silico prediction, not a clinical call.

CCDC17 p.Ala195Ser

c.583G>T · VCV4220813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0972	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.63	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 -2.7, phastCons 0.005
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	5.007	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC17
Protein: p.Ala195Ser
Coding: c.583G>T
MANE Select: NM_001114938
Type: single nucleotide variant
Location: chr1:45623028 (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.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
CCDC17 p.Ala487Thr 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-ala195ser (accessed [today's date]).

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