Is CDV3 p.Pro58Leu (c.173C>T) pathogenic?

CDV3 p.Pro58Leu (c.173C>T) is classified Uncertain significance in CDV3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely benign (0.1301); Very rare (popmax 0.00607%, amr).

How common is CDV3 p.Pro58Leu (c.173C>T) in the general population?

CDV3 p.Pro58Leu (c.173C>T) is very rare (popmax 0.00607%, amr) (gnomAD).

What do computational predictors say about CDV3 p.Pro58Leu (c.173C>T)?

AlphaMissense predicts likely benign (score 0.1301) — an in-silico prediction, not a clinical call.

CDV3 p.Pro58Leu

c.173C>T · rs2074711385 · VCV2532691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1301 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00607%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1301	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -1.3, phastCons 0.98
Regional constraint	o/e 1.08	unconstrained · MANE · 13 kb · p 0.28 · regional, not allelic
Overall
CADD	19.79	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00607% Admixed American · 1/16,466 alleles

Overall 0.00136% 2/146,922 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00607%	16,466
African / African-American	0.00175%	57,056

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: CDV3
Protein: p.Pro58Leu
Coding: c.173C>T
MANE Select: NM_017548
dbSNP: rs2074711385
Type: single nucleotide variant
Location: chr3:133574217 (GRCh38)
Gene constraint: LOEUF 1.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.82
Residue 58: the 'disordered' region

Full CDV3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDV3 p.Ala145Gly Uncertain significance ★ ⚠ same type
CDV3 p.Ala149Val Uncertain significance ★ ⚠ same type
CDV3 p.Ala35Val Uncertain significance ★ ⚠ same type
CDV3 p.Ala52Val Uncertain significance ★ ⚠ same type
CDV3 p.Ala68Gly Uncertain significance ★ ⚠ same type
CDV3 p.Ala68Pro Uncertain significance ★ ⚠ same type
CDV3 p.Ala73Val Uncertain significance ★ ⚠ same type
CDV3 p.Arg117Gly 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/cdv3-p-pro58leu (accessed [today's date]).

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