Is CCDC17 p.Gly397Ser (c.1189G>A) pathogenic?

CCDC17 p.Gly397Ser (c.1189G>A) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: ambiguous (0.5214); Very rare (popmax 0.00182%, amr).

How common is CCDC17 p.Gly397Ser (c.1189G>A) in the general population?

CCDC17 p.Gly397Ser (c.1189G>A) is very rare (popmax 0.00182%, amr) (gnomAD).

What do computational predictors say about CCDC17 p.Gly397Ser (c.1189G>A)?

AlphaMissense predicts ambiguous (score 0.5214) — an in-silico prediction, not a clinical call.

CCDC17 p.Gly397Ser

c.1189G>A · VCV3996680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5214 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00182%, amr)

Computational evidence

Protein change
AlphaMissense	0.5214	ambiguous · top 10% in CCDC17
REVEL	0.608	indeterminate
SaProt	LLR -12.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	26.5	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 0.00182% Admixed American · 1/54,962 alleles

Filtering AF 0.000622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00048%

Overall 0.000884% 14/1,583,986 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00182%	54,962
European (non-Finnish)	0.00112%	89,661

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.Gly397Ser
Coding: c.1189G>A
MANE Select: NM_001114938
Type: single nucleotide variant
Location: chr1:45621480 (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-gly397ser (accessed [today's date]).

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