Is CCDC92 p.Pro193Leu (c.578C>T) pathogenic?

CCDC92 p.Pro193Leu (c.578C>T) is classified Uncertain significance in CCDC92 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: ambiguous (0.3534); Very rare (popmax 0.000424%, nfe).

How common is CCDC92 p.Pro193Leu (c.578C>T) in the general population?

CCDC92 p.Pro193Leu (c.578C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CCDC92 p.Pro193Leu (c.578C>T)?

AlphaMissense predicts ambiguous (score 0.3534) — an in-silico prediction, not a clinical call.

CCDC92 p.Pro193Leu

c.578C>T · VCV3487175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3534 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3534	ambiguous
REVEL	0.307	indeterminate
SaProt	LLR -6.56	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,244 bp · p 0.054 · regional, not allelic
Overall
CADD	27.9	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 0.000424% European (non-Finnish) · 5/1,179,998 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,006 alleles · very rare

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: CCDC92
Protein: p.Pro193Leu
Coding: c.578C>T
MANE Select: NM_025140
Type: single nucleotide variant
Location: chr12:123937476 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI 0.25 (gnomAD)
Structure: AlphaFold pLDDT 73.80
Residue 193: the 'disordered' region

Full CCDC92 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC92 p.Ala114Thr Uncertain significance ★ ⚠ same type
CCDC92 p.Ala178Asp Uncertain significance ★ ⚠ same type
CCDC92 p.Ala226Val Uncertain significance ★ ⚠ same type
CCDC92 p.Ala269Thr Uncertain significance ★ ⚠ same type
CCDC92 p.Ala93Val Uncertain significance ★ ⚠ same type
CCDC92 p.Arg203His Uncertain significance ★ ⚠ same type
CCDC92 p.Arg223Gly Uncertain significance ★ ⚠ same type
CCDC92 p.Arg234Gln 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/ccdc92-p-pro193leu (accessed [today's date]).

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