Is CCDC9 p.Gly203Arg (c.607G>A) pathogenic?

CCDC9 p.Gly203Arg (c.607G>A) is classified Uncertain significance in CCDC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: ambiguous (0.4366); Ultra-rare (popmax 0.07%, amr).

How common is CCDC9 p.Gly203Arg (c.607G>A) in the general population?

CCDC9 p.Gly203Arg (c.607G>A) is ultra-rare (popmax 0.07%, amr) (gnomAD).

What do computational predictors say about CCDC9 p.Gly203Arg (c.607G>A)?

AlphaMissense predicts ambiguous (score 0.4366) — an in-silico prediction, not a clinical call.

CCDC9 p.Gly203Arg

c.607G>A · VCV4221798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4366 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.07%, amr)

Computational evidence

Protein change
AlphaMissense	0.4366	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -4.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 4.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.0052 · regional, not allelic
Overall
CADD	22.5	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 0.07% Admixed American · 38/54,274 alleles

Filtering AF 0.0523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0463%

Overall 0.0145% 226/1,554,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.07%	1,428
Remaining individualsnot grpmax-eligible	0.0317%	3,154
East Asian	0.0272%	3,680
European (non-Finnish)	0.0134%	7,461
Finnishnot grpmax-eligible	0.00169%	59,148
African / African-American	0.00135%	73,854
South Asian	0.00123%	81,464

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.Gly203Arg
Coding: c.607G>A
MANE Select: NM_015603
Type: single nucleotide variant
Location: chr19:47264833 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.06
Residue 203: 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-gly203arg (accessed [today's date]).

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