Is CNDP2 p.Pro155Ser (c.463C>T) pathogenic?

CNDP2 p.Pro155Ser (c.463C>T) is classified Uncertain significance in CNDP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.6456); Very rare (popmax 0.00401%, afr).

How common is CNDP2 p.Pro155Ser (c.463C>T) in the general population?

CNDP2 p.Pro155Ser (c.463C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CNDP2 p.Pro155Ser (c.463C>T)?

AlphaMissense predicts likely pathogenic (score 0.6456) — an in-silico prediction, not a clinical call.

CNDP2 p.Pro155Ser

c.463C>T · rs148388345 · VCV3146419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6456 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6456	likely pathogenic
REVEL	0.358	indeterminate
SaProt	LLR -13.50	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.55 · regional, not allelic
Overall
CADD	24.0	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 0.00401% African / African-American · 3/74,878 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,146 alleles · very rare exomes 3/1,460,956 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,959
East Asian	0.00223%	44,886

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: CNDP2
Protein: p.Pro155Ser
Coding: c.463C>T
MANE Select: NM_018235
dbSNP: rs148388345
Type: single nucleotide variant
Location: chr18:74510819 (GRCh38)
Gene constraint: LOEUF 0.916 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.84 · 1 PDB
Residue 155: 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-pro155ser (accessed [today's date]).

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