Is CCDC17 p.Pro394Arg (c.1181C>G) pathogenic?

CCDC17 p.Pro394Arg (c.1181C>G) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.2623); Rare (popmax 0.677%, mid).

How common is CCDC17 p.Pro394Arg (c.1181C>G) in the general population?

CCDC17 p.Pro394Arg (c.1181C>G) is rare (popmax 0.677%, mid) (gnomAD).

What do computational predictors say about CCDC17 p.Pro394Arg (c.1181C>G)?

AlphaMissense predicts likely benign (score 0.2623) — an in-silico prediction, not a clinical call.

CCDC17 p.Pro394Arg

c.1181C>G · rs201021595 · VCV2371726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2623 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.677%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2623	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -11.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	26.3	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 0.677% Middle Eastern · 41/6,058 alleles

Filtering AF 0.513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.455%

Overall 0.0285% 460/1,613,624 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.677%	148
Ashkenazi Jewishnot grpmax-eligible	0.426%	235
South Asian	0.1%	1,000
Remaining individualsnot grpmax-eligible	0.0704%	1,420
Admixed American	0.0383%	2,608
African / African-American	0.0147%	6,821
European (non-Finnish)	0.0105%	9,514

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.Pro394Arg
Coding: c.1181C>G
MANE Select: NM_001114938
dbSNP: rs201021595
Type: single nucleotide variant
Location: chr1:45621641 (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-pro394arg (accessed [today's date]).

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