Is CCDC9 p.Arg201His (c.602G>A) pathogenic?

CCDC9 p.Arg201His (c.602G>A) is classified Uncertain significance in CCDC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: likely benign (0.1488); Ultra-rare (popmax 0.0516%, mid).

How common is CCDC9 p.Arg201His (c.602G>A) in the general population?

CCDC9 p.Arg201His (c.602G>A) is ultra-rare (popmax 0.0516%, mid) (gnomAD).

What do computational predictors say about CCDC9 p.Arg201His (c.602G>A)?

AlphaMissense predicts likely benign (score 0.1488) — an in-silico prediction, not a clinical call.

CCDC9 p.Arg201His

c.602G>A · VCV3828928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1488 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0516%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1488	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -7.87	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 11	GERP 5.3, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.0052 · regional, not allelic
Overall
CADD	24.4	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 0.0516% Middle Eastern · 3/5,814 alleles

Filtering AF 0.014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00748%

Overall 0.00141% 22/1,555,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0516%	1,938
Admixed American	0.00367%	27,216
Remaining individualsnot grpmax-eligible	0.00334%	29,980
South Asian	0.00244%	40,995
East Asian	0.00226%	44,212
European (non-Finnish)	0.00104%	95,816

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.Arg201His
Coding: c.602G>A
MANE Select: NM_015603
Type: single nucleotide variant
Location: chr19:47264828 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.06
Residue 201: 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-arg201his (accessed [today's date]).

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