Is NCAPD3 p.Pro63Arg (c.188C>G) pathogenic?

NCAPD3 p.Pro63Arg (c.188C>G) is classified Uncertain significance in NCAPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely benign (0.1333); Very rare (popmax 0.00017%, nfe).

How common is NCAPD3 p.Pro63Arg (c.188C>G) in the general population?

NCAPD3 p.Pro63Arg (c.188C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about NCAPD3 p.Pro63Arg (c.188C>G)?

AlphaMissense predicts likely benign (score 0.1333) — an in-silico prediction, not a clinical call.

NCAPD3 p.Pro63Arg

c.188C>G · VCV3917737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1333	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -11.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.1	GERP -1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,944 bp · p 0.8 · regional, not allelic
Overall
CADD	19.78	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,868 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,898 alleles · very rare exomes 2/1,461,646 · genomes 0/152,252 · joint denominator

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: NCAPD3
Protein: p.Pro63Arg
Coding: c.188C>G
MANE Select: NM_015261
Type: single nucleotide variant
Location: chr11:134220603 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.29 · 1 PDB

Full NCAPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NCAPD3 c.4388+1G>A Likely pathogenic ★★ same type
NCAPD3 p.Ala334Thr Uncertain significance ★★ ⚠ same type
NCAPD3 p.Arg519Cys Uncertain significance ★★ ⚠ same type
NCAPD3 p.Gly1451Arg Uncertain significance ★★ ⚠ same type
NCAPD3 p.Lys221Asn Uncertain significance ★★ ⚠ same type
NCAPD3 c.1090-33A>G Benign ★★ same type
NCAPD3 c.1215+28G>A Benign ★★ same type
NCAPD3 c.1525+18T>A Benign ★★ 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/ncapd3-p-pro63arg (accessed [today's date]).

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