Is CCDC9 p.Arg232Cys (c.694C>T) pathogenic?

CCDC9 p.Arg232Cys (c.694C>T) is classified Uncertain significance in CCDC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: ambiguous (0.3608); Very rare (popmax 0.00284%, afr).

How common is CCDC9 p.Arg232Cys (c.694C>T) in the general population?

CCDC9 p.Arg232Cys (c.694C>T) is very rare (popmax 0.00284%, afr) (gnomAD).

What do computational predictors say about CCDC9 p.Arg232Cys (c.694C>T)?

AlphaMissense predicts ambiguous (score 0.3608) — an in-silico prediction, not a clinical call.

CCDC9 p.Arg232Cys

c.694C>T · rs763363009 · VCV2562594

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3608 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00284%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3608	ambiguous
REVEL	0.256	benign-leaning
SaProt	LLR -9.46	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.79 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 5.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.0052 · regional, not allelic
Overall
CADD	28.6	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 0.00284% African / African-American · 2/70,486 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00115%

Overall 0.00219% 32/1,458,424 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00623%	16,063
Remaining individualsnot grpmax-eligible	0.00534%	18,716
African / African-Americangrpmax	0.00284%	35,243
East Asian	0.00241%	41,410
European (non-Finnish)	0.00207%	48,218

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg232Cys
Coding: c.694C>T
MANE Select: NM_015603
dbSNP: rs763363009
Type: single nucleotide variant
Location: chr19:47264920 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.06
Residue 232: the 'disordered' region

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

Similar variants

CCDC9 p.Ala15Val Uncertain significance ★ ⚠ same type
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

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-arg232cys (accessed [today's date]).

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