Is CNDP2 p.Lys375Arg (c.1124A>G) pathogenic?

CNDP2 p.Lys375Arg (c.1124A>G) is classified Uncertain significance in CNDP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.067); Absent from gnomAD v4.1.

How common is CNDP2 p.Lys375Arg (c.1124A>G) in the general population?

CNDP2 p.Lys375Arg (c.1124A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNDP2 p.Lys375Arg (c.1124A>G)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

CNDP2 p.Lys375Arg

c.1124A>G · VCV4654861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -7.42	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 3.8	GERP -0.31, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.55 · regional, not allelic
Overall
CADD	18.68	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

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: CNDP2
Protein: p.Lys375Arg
Coding: c.1124A>G
MANE Select: NM_018235
Type: single nucleotide variant
Location: chr18:74518554 (GRCh38)
Gene constraint: LOEUF 0.916 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.84 · 1 PDB
Residue 375: a β-strand

Full CNDP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNDP2 p.Thr403Ala Uncertain significance ★★ ⚠ same type
CNDP2 c.1211-8C>A Benign ★★ same type
CNDP2 p.Pro35Leu Benign ★★ ⚠ same type
CNDP2 p.Ala23Ser Uncertain significance ★ ⚠ same type
CNDP2 p.Ala268Thr Uncertain significance ★ ⚠ same type
CNDP2 p.Ala2Val Uncertain significance ★ ⚠ same type
CNDP2 p.Ala322Gly Uncertain significance ★ ⚠ same type
CNDP2 p.Ala322Thr 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/cndp2-p-lys375arg (accessed [today's date]).

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