Is CCDC93 p.Leu281Pro (c.842T>C) pathogenic?

CCDC93 p.Leu281Pro (c.842T>C) is classified Uncertain significance in CCDC93 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.904); Absent from gnomAD v4.1.

How common is CCDC93 p.Leu281Pro (c.842T>C) in the general population?

CCDC93 p.Leu281Pro (c.842T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC93 p.Leu281Pro (c.842T>C)?

AlphaMissense predicts likely pathogenic (score 0.904) — an in-silico prediction, not a clinical call.

CCDC93 p.Leu281Pro

c.842T>C · VCV4649856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.904 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.904	likely pathogenic
REVEL	0.36	indeterminate
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 94 kb · p 0.0042 · regional, not allelic
Overall
CADD	28.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC93
Protein: p.Leu281Pro
Coding: c.842T>C
MANE Select: NM_019044
Type: single nucleotide variant
Location: chr2:117973954 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.49 · 4 PDB
Residue 281: the 'sufficient for interaction with ccdc22' region; an α-helix

Full CCDC93 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC93 p.Pro228Leu Benign ★★ same type
CCDC93 p.Ala226Val Uncertain significance ★ ⚠ same type
CCDC93 p.Ala262Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala272Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala370Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala510Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala628Val Uncertain significance ★ ⚠ same type
CCDC93 p.Arg126Gly 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/ccdc93-p-leu281pro (accessed [today's date]).

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