Is NCAPD3 p.Pro173= (c.519C>T) pathogenic?

NCAPD3 p.Pro173= (c.519C>T) is classified Likely benign in NCAPD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-10-07). Ultra-rare (popmax 0.0694%, afr); Associated with NCAPD3-related disorder.

What condition is associated with NCAPD3 p.Pro173= (c.519C>T)?

NCAPD3 p.Pro173= (c.519C>T) is associated with NCAPD3-related disorder (ClinVar).

How common is NCAPD3 p.Pro173= (c.519C>T) in the general population?

NCAPD3 p.Pro173= (c.519C>T) is ultra-rare (popmax 0.0694%, afr) (gnomAD).

NCAPD3 p.Pro173=

c.519C>T · rs149186393 · VCV3054771

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0694%, afr)

Conditions

NCAPD3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -2.2
Overall
CADD	4.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0694% African / African-American · 52/74,980 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0489%

Overall 0.00613% 99/1,613,972 alleles · ultra-rare exomes 63/1,461,818 · genomes 36/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0694%	1,442
East Asian	0.0312%	3,205
Admixed American	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.008%	12,500
European (non-Finnish)	0.00186%	53,635

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.Pro173=
Coding: c.519C>T
MANE Select: NM_015261
dbSNP: rs149186393
Type: single nucleotide variant
Location: chr11:134210318 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.29 · 1 PDB
Residue 173: the 'disordered' region

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

Disease context

NCAPD3-related disorder

Similar variants

NCAPD3 p.Pro173Leu Uncertain significance ★ ⚠ same residue
NCAPD3 p.Lys221Asn Uncertain significance ★★ ⚠ same condition
NCAPD3 c.3573+3G>A Likely benign ★ same condition
NCAPD3 c.1525+6G>C Likely benign same condition
NCAPD3 c.1616-4A>G Likely benign same condition
NCAPD3 c.2046-5T>C Likely benign same condition
NCAPD3 c.2675-4G>A Likely benign same condition
NCAPD3 c.4253-7T>C Likely benign same condition

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-pro173 (accessed [today's date]).

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