Is CCDC183 p.Leu332Pro (c.995T>C) pathogenic?

CCDC183 p.Leu332Pro (c.995T>C) is classified Uncertain significance in CCDC183 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely pathogenic (0.6398); Ultra-rare (popmax 0.0116%, amr).

How common is CCDC183 p.Leu332Pro (c.995T>C) in the general population?

CCDC183 p.Leu332Pro (c.995T>C) is ultra-rare (popmax 0.0116%, amr) (gnomAD).

What do computational predictors say about CCDC183 p.Leu332Pro (c.995T>C)?

AlphaMissense predicts likely pathogenic (score 0.6398) — an in-silico prediction, not a clinical call.

CCDC183 p.Leu332Pro

c.995T>C · rs774753826 · VCV3138987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6398 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6398	likely pathogenic · top 4% in CCDC183
REVEL	0.281	benign-leaning
SaProt	LLR -13.91	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 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 11 kb · p 0.0024 · regional, not allelic
Overall
CADD	27.3	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 0.0116% Admixed American · 6/51,598 alleles

Filtering AF 0.00497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00343%

Overall 0.00328% 51/1,556,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0116%	8,600
South Asian	0.00592%	16,900
European (non-Finnish)	0.00339%	29,479
Remaining individualsnot grpmax-eligible	0.00166%	60,268

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.Leu332Pro
Coding: c.995T>C
MANE Select: NM_001039374
dbSNP: rs774753826
Type: single nucleotide variant
Location: chr9:136806124 (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-leu332pro (accessed [today's date]).

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