Is CCDC15 p.Pro147Arg (c.440C>G) pathogenic?

CCDC15 p.Pro147Arg (c.440C>G) is classified Uncertain significance in CCDC15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.2005); Rare (popmax 0.114%, sas).

How common is CCDC15 p.Pro147Arg (c.440C>G) in the general population?

CCDC15 p.Pro147Arg (c.440C>G) is rare (popmax 0.114%, sas) (gnomAD).

What do computational predictors say about CCDC15 p.Pro147Arg (c.440C>G)?

AlphaMissense predicts likely benign (score 0.2005) — an in-silico prediction, not a clinical call.

CCDC15 p.Pro147Arg

c.440C>G · VCV4649148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2005 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2005	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -7.26	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 0.47	GERP 0.52
Regional constraint	o/e 1.01	unconstrained · MANE · 86 kb · p 0.73 · regional, not allelic
Overall
CADD	14.32	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 0.114% South Asian · 99/87,120 alleles

Filtering AF 0.0955% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0887%

Overall 0.0063% 100/1,586,568 alleles · rare exomes 94/1,434,418 · genomes 6/152,150 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.114%	880
Remaining individualsnot grpmax-eligible	0.00162%	61,542

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: CCDC15
Protein: p.Pro147Arg
Coding: c.440C>G
MANE Select: NM_025004
Type: single nucleotide variant
Location: chr11:124959927 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.02

Full CCDC15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC15 p.Pro147Ala Uncertain significance ★ ⚠ same residue
CCDC15 p.Arg181Cys Uncertain significance ★★ ⚠ same type
CCDC15 p.Pro10= Benign ★★ same type
CCDC15 p.Ala110Thr Uncertain significance ★ ⚠ same type
CCDC15 p.Ala140Val Uncertain significance ★ ⚠ same type
CCDC15 p.Ala19Thr Uncertain significance ★ ⚠ same type
CCDC15 p.Ala44Ser Uncertain significance ★ ⚠ same type
CCDC15 p.Ala44Val 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/ccdc15-p-pro147arg (accessed [today's date]).

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