Is CCDC15 p.Asp573Val (c.1718A>T) pathogenic?

CCDC15 p.Asp573Val (c.1718A>T) is classified Uncertain significance in CCDC15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: ambiguous (0.3831); Very rare (popmax 0.000593%, nfe).

How common is CCDC15 p.Asp573Val (c.1718A>T) in the general population?

CCDC15 p.Asp573Val (c.1718A>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CCDC15 p.Asp573Val (c.1718A>T)?

AlphaMissense predicts ambiguous (score 0.3831) — an in-silico prediction, not a clinical call.

CCDC15 p.Asp573Val

c.1718A>T · VCV4649161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3831 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3831	ambiguous
REVEL	0.067	moderately benign-leaning
SaProt	LLR -12.50	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -1.7, phastCons 0.004
Regional constraint	o/e 1.01	unconstrained · MANE · 86 kb · p 0.73 · regional, not allelic
Overall
CADD	13.24	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 0.000593% European (non-Finnish) · 7/1,179,856 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,648 alleles · very rare

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.Asp573Val
Coding: c.1718A>T
MANE Select: NM_025004
Type: single nucleotide variant
Location: chr11:124987944 (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.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
CCDC15 p.Ala6Thr 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-asp573val (accessed [today's date]).

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