Is CDV3 p.Gly49Asp (c.146G>A) pathogenic?

CDV3 p.Gly49Asp (c.146G>A) is classified Uncertain significance in CDV3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely benign (0.3223); Ultra-rare (popmax 0.0192%, nfe).

How common is CDV3 p.Gly49Asp (c.146G>A) in the general population?

CDV3 p.Gly49Asp (c.146G>A) is ultra-rare (popmax 0.0192%, nfe) (gnomAD).

What do computational predictors say about CDV3 p.Gly49Asp (c.146G>A)?

AlphaMissense predicts likely benign (score 0.3223) — an in-silico prediction, not a clinical call.

CDV3 p.Gly49Asp

c.146G>A · VCV3831078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3223 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0192%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3223	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -9.79	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 5.3	GERP -1.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 13 kb · p 0.28 · regional, not allelic
Overall
CADD	22.9	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 0.0192% European (non-Finnish) · 165/858,420 alleles

Filtering AF 0.0168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0159%

Overall 0.0166% 170/1,021,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0192%	5,203
Admixed American	0.012%	8,356
Finnishnot grpmax-eligible	0.0086%	11,630
Remaining individualsnot grpmax-eligible	0.00636%	15,718

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.Gly49Asp
Coding: c.146G>A
MANE Select: NM_017548
Type: single nucleotide variant
Location: chr3:133574190 (GRCh38)
Gene constraint: LOEUF 1.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.82
Residue 49: 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-gly49asp (accessed [today's date]).

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