Is CNDP1 p.Ala429Pro (c.1285G>C) pathogenic?

CNDP1 p.Ala429Pro (c.1285G>C) is classified Uncertain significance in CNDP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely pathogenic (0.8252); Very rare (popmax 0.00119%, nfe).

How common is CNDP1 p.Ala429Pro (c.1285G>C) in the general population?

CNDP1 p.Ala429Pro (c.1285G>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about CNDP1 p.Ala429Pro (c.1285G>C)?

AlphaMissense predicts likely pathogenic (score 0.8252) — an in-silico prediction, not a clinical call.

CNDP1 p.Ala429Pro

c.1285G>C · rs138535410 · VCV2471793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8252 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8252	likely pathogenic
REVEL	0.72	pathogenic-leaning
SaProt	LLR -13.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 50 kb · p 0.13 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00119% European (non-Finnish) · 14/1,180,016 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,614,018 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: CNDP1
Protein: p.Ala429Pro
Coding: c.1285G>C
MANE Select: NM_032649
dbSNP: rs138535410
Type: single nucleotide variant
Location: chr18:74580247 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.16 · 1 PDB
Residue 429: an α-helix

Full CNDP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNDP1 p.Ala238Val Benign/Likely benign ★★ same type
CNDP1 p.Ala355Thr Benign ★★ ⚠ same type
CNDP1 p.Ile434Val Benign ★★ same type
CNDP1 p.Pro417Ser Benign ★★ ⚠ same type
CNDP1 p.Val466Leu Benign ★★ same type
CNDP1 p.Ala10Val Uncertain significance ★ ⚠ same type
CNDP1 p.Ala163Val Uncertain significance ★ ⚠ same type
CNDP1 p.Ala238Gly 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/cndp1-p-ala429pro (accessed [today's date]).

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