Is CCDC9 p.Ala15Val (c.44C>T) pathogenic?

CCDC9 p.Ala15Val (c.44C>T) is classified Uncertain significance in CCDC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). AlphaMissense: ambiguous (0.4202); Very rare (popmax 0.00333%, amr).

How common is CCDC9 p.Ala15Val (c.44C>T) in the general population?

CCDC9 p.Ala15Val (c.44C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CCDC9 p.Ala15Val (c.44C>T)?

AlphaMissense predicts ambiguous (score 0.4202) — an in-silico prediction, not a clinical call.

CCDC9 p.Ala15Val

c.44C>T · rs2059026262 · VCV3139614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4202 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4202	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -9.72	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 5.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.0052 · regional, not allelic
Overall
CADD	26.2	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 0.00333% Admixed American · 2/59,986 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000248% 4/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,993
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00134%	74,900

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: CCDC9
Protein: p.Ala15Val
Coding: c.44C>T
MANE Select: NM_015603
dbSNP: rs2059026262
Type: single nucleotide variant
Location: chr19:47258599 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.06

Full CCDC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC9 p.Ala175Thr Uncertain significance ★ ⚠ same type
CCDC9 p.Ala322Val Uncertain significance ★ ⚠ same type
CCDC9 p.Ala356Ser Uncertain significance ★ ⚠ same type
CCDC9 p.Ala360Val Uncertain significance ★ ⚠ same type
CCDC9 p.Ala405Val Uncertain significance ★ ⚠ same type
CCDC9 p.Ala455Val Uncertain significance ★ ⚠ same type
CCDC9 p.Ala525Ser Uncertain significance ★ ⚠ same type
CCDC9 p.Arg102Gln 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/ccdc9-p-ala15val (accessed [today's date]).

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