Is CCDC88C p.Pro2009= (c.6027G>A) pathogenic?

CCDC88C p.Pro2009= (c.6027G>A) is classified Benign/Likely benign in CCDC88C (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.328%, sas); Associated with hydrocephalus, nonsyndromic, autosomal recessive 1.

How common is CCDC88C p.Pro2009= (c.6027G>A) in the general population?

CCDC88C p.Pro2009= (c.6027G>A) is rare (popmax 0.328%, sas) (gnomAD).

CCDC88C p.Pro2009=

Q: What condition is associated with CCDC88C p.Pro2009= (c.6027G>A)?

CCDC88C p.Pro2009= (c.6027G>A) is associated with hydrocephalus, nonsyndromic, autosomal recessive 1, spinocerebellar ataxia type 40 (ClinVar).

c.6027G>A · rs200979954 · VCV708836

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.328%, sas)

Conditions

hydrocephalus, nonsyndromic, autosomal recessive 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -4
Overall
CADD	0.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.328% South Asian · 299/91,030 alleles

Filtering AF 0.298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.286%

Overall 0.231% 3,727/1,611,708 alleles · rare exomes 3,469/1,459,376 · genomes 258/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.328%	304
European (non-Finnish)	0.26%	385
Remaining individualsnot grpmax-eligible	0.178%	562
Finnishnot grpmax-eligible	0.169%	591
Admixed American	0.167%	600
Middle Eastern	0.0678%	1,475
African / African-American	0.048%	2,085
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,934

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: CCDC88C
Protein: p.Pro2009=
Coding: c.6027G>A
MANE Select: NM_001080414
dbSNP: rs200979954
Type: single nucleotide variant
Location: chr14:91272685 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.69
Residue 2009: the 'disordered' region

Full CCDC88C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hydrocephalus, nonsyndromic, autosomal recessive 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spinocerebellar ataxia type 40

Similar variants

CCDC88C p.Pro2009Leu Uncertain significance ★★ ⚠ same residue
CCDC88C c.3358-2A>C Likely pathogenic ★★ same condition
CCDC88C c.4442-2A>G Likely pathogenic ★★ same condition
CCDC88C c.4768+1G>T Likely pathogenic ★★ same condition
CCDC88C p.Arg1701Ter Pathogenic/Likely pathogenic ★★ same condition
CCDC88C p.Arg312Ter Pathogenic ★★ same condition
CCDC88C c.3358-5G>A Uncertain significance ★★ same condition
CCDC88C p.Ala583Val Uncertain significance ★★ ⚠ same condition

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/ccdc88c-p-pro2009 (accessed [today's date]).

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