Is CCDC183 p.Leu196Pro (c.587T>C) pathogenic?

CCDC183 p.Leu196Pro (c.587T>C) is classified Uncertain significance in CCDC183 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.7669); Ultra-rare (popmax 0.0467%, afr).

How common is CCDC183 p.Leu196Pro (c.587T>C) in the general population?

CCDC183 p.Leu196Pro (c.587T>C) is ultra-rare (popmax 0.0467%, afr) (gnomAD).

What do computational predictors say about CCDC183 p.Leu196Pro (c.587T>C)?

AlphaMissense predicts likely pathogenic (score 0.7669) — an in-silico prediction, not a clinical call.

CCDC183 p.Leu196Pro

c.587T>C · rs375780777 · VCV3138980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7669 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7669	likely pathogenic · top 2% in CCDC183
REVEL	0.175	moderately benign-leaning
SaProt	LLR -10.87	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.59, phastCons 0.23
Regional constraint	o/e 1.12	unconstrained · MANE · 11 kb · p 0.0024 · regional, not allelic
Overall
CADD	18.77	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 0.0467% African / African-American · 35/74,938 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0303%

Overall 0.00254% 41/1,613,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0467%	2,141
Remaining individualsnot grpmax-eligible	0.0064%	15,616
Admixed American	0.00167%	59,972
European (non-Finnish)	8.48e-05%	1,179,889

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.Leu196Pro
Coding: c.587T>C
MANE Select: NM_001039374
dbSNP: rs375780777
Type: single nucleotide variant
Location: chr9:136802707 (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-leu196pro (accessed [today's date]).

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