Is CDON p.Pro172Ser (c.514C>T) pathogenic?

CDON p.Pro172Ser (c.514C>T) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: ambiguous (0.4335); Absent from gnomAD v4.1.

How common is CDON p.Pro172Ser (c.514C>T) in the general population?

CDON p.Pro172Ser (c.514C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDON p.Pro172Ser (c.514C>T)?

AlphaMissense predicts ambiguous (score 0.4335) — an in-silico prediction, not a clinical call.

CDON p.Pro172Ser

c.514C>T · VCV4084573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4335 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4335	ambiguous
REVEL	0.485	indeterminate
SaProt	LLR -8.38	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	24.6	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: CDON
Protein: p.Pro172Ser
Coding: c.514C>T
MANE Select: NM_001378964
Type: single nucleotide variant
Location: chr11:126018456 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 172: the ig-like c2-type 2 domain

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

Similar variants

CDON c.3276+1G>T Uncertain significance ★★ same type
CDON c.640+1G>A Uncertain significance ★★ same type
CDON c.*1805A>G Uncertain significance ★★ same type
CDON c.*1816C>T Uncertain significance ★★ same type
CDON c.*2349A>C Uncertain significance ★★ same type
CDON c.*2377T>C Uncertain significance ★★ same type
CDON c.*2760A>G Uncertain significance ★★ same type
CDON p.Ala1099Val 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/cdon-p-pro172ser (accessed [today's date]).

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