Is CCDC17 p.Leu440Arg (c.1319T>G) pathogenic?

CCDC17 p.Leu440Arg (c.1319T>G) is classified Uncertain significance in CCDC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely benign (0.3061); Very rare (popmax 0.00803%, afr).

How common is CCDC17 p.Leu440Arg (c.1319T>G) in the general population?

CCDC17 p.Leu440Arg (c.1319T>G) is very rare (popmax 0.00803%, afr) (gnomAD).

What do computational predictors say about CCDC17 p.Leu440Arg (c.1319T>G)?

AlphaMissense predicts likely benign (score 0.3061) — an in-silico prediction, not a clinical call.

CCDC17 p.Leu440Arg

c.1319T>G · rs1444929495 · VCV2350025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3061 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00803%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3061	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -5.41	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,631 bp · p 0.23 · regional, not allelic
Overall
CADD	25.2	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 0.00803% African / African-American · 6/74,676 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000695% 10/1,438,248 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00803%	12,446
Remaining individualsnot grpmax-eligible	0.00648%	15,435

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.Leu440Arg
Coding: c.1319T>G
MANE Select: NM_001114938
dbSNP: rs1444929495
Type: single nucleotide variant
Location: chr1:45621350 (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-leu440arg (accessed [today's date]).

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