Is CCDC9 p.Thr83Pro (c.247A>C) pathogenic?

CCDC9 p.Thr83Pro (c.247A>C) is classified Uncertain significance in CCDC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.076); Low-frequency (popmax 1.11%, sas).

How common is CCDC9 p.Thr83Pro (c.247A>C) in the general population?

CCDC9 p.Thr83Pro (c.247A>C) is low-frequency (popmax 1.11%, sas) (gnomAD).

What do computational predictors say about CCDC9 p.Thr83Pro (c.247A>C)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

CCDC9 p.Thr83Pro

c.247A>C · VCV4221780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.39	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 2.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.0052 · regional, not allelic
Overall
CADD	16.73	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 1.11% South Asian · 858/77,092 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0593% 904/1,523,488 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.11%	90
Remaining individualsnot grpmax-eligible	0.063%	1,588
Middle Eastern	0.0436%	2,294
East Asian	0.00226%	44,224
Admixed American	0.00215%	46,442
African / African-American	0.00139%	71,980
European (non-Finnish)	0.000349%	286,257

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.Thr83Pro
Coding: c.247A>C
MANE Select: NM_015603
Type: single nucleotide variant
Location: chr19:47260624 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.06
Residue 83: the 'disordered' region

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

Similar variants

INAFM1 p.Pro83Leu Uncertain significance ★ ⚠ same residue
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

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-thr83pro (accessed [today's date]).

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