Is CCDC183 p.Arg27Pro (c.80G>C) pathogenic?

CCDC183 p.Arg27Pro (c.80G>C) is classified Uncertain significance in CCDC183 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely pathogenic (0.6445); Ultra-rare (popmax 0.0325%, nfe).

How common is CCDC183 p.Arg27Pro (c.80G>C) in the general population?

CCDC183 p.Arg27Pro (c.80G>C) is ultra-rare (popmax 0.0325%, nfe) (gnomAD).

What do computational predictors say about CCDC183 p.Arg27Pro (c.80G>C)?

AlphaMissense predicts likely pathogenic (score 0.6445) — an in-silico prediction, not a clinical call.

CCDC183 p.Arg27Pro

c.80G>C · rs200895085 · VCV2459063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6445 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0325%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6445	likely pathogenic · top 4% in CCDC183
REVEL	0.241	benign-leaning
SaProt	LLR -11.33	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP -2.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 11 kb · p 0.0024 · 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 0.0325% European (non-Finnish) · 383/1,179,764 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.0252% 407/1,613,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0325%	3,080
Remaining individualsnot grpmax-eligible	0.024%	4,163
Admixed American	0.005%	19,989
African / African-American	0.004%	24,973
South Asian	0.0033%	30,339

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: CCDC183
Protein: p.Arg27Pro
Coding: c.80G>C
MANE Select: NM_001039374
dbSNP: rs200895085
Type: single nucleotide variant
Location: chr9:136799111 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.98

Full CCDC183 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC183 p.Gln296Ter Likely pathogenic ★ same type
CCDC183 p.Ala238Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Ala348Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Ala392Val Uncertain significance ★ ⚠ same type
CCDC183 p.Ala424Glu Uncertain significance ★ ⚠ same type
CCDC183 p.Ala518Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Arg117Pro Uncertain significance ★ ⚠ same type
CCDC183 p.Arg132Gly 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/ccdc183-p-arg27pro (accessed [today's date]).

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