Is NCAPD3 p.Ala884Val (c.2651C>T) pathogenic?

NCAPD3 p.Ala884Val (c.2651C>T) is classified Uncertain significance in NCAPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.115); Ultra-rare (popmax 0.0761%, afr).

How common is NCAPD3 p.Ala884Val (c.2651C>T) in the general population?

NCAPD3 p.Ala884Val (c.2651C>T) is ultra-rare (popmax 0.0761%, afr) (gnomAD).

What do computational predictors say about NCAPD3 p.Ala884Val (c.2651C>T)?

AlphaMissense predicts likely benign (score 0.115) — an in-silico prediction, not a clinical call.

NCAPD3 p.Ala884Val

c.2651C>T · rs139400293 · VCV2217101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.115 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0761%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.115	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -4.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 57 kb · p 0.0017 · regional, not allelic
Overall
CADD	24.3	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

Grpmax group 0.0761% African / African-American · 57/74,934 alleles

Filtering AF 0.0602% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0545%

Overall 0.00366% 59/1,614,024 alleles · ultra-rare exomes 23/1,461,832 · genomes 36/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0761%	1,315
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ala884Val
Coding: c.2651C>T
MANE Select: NM_015261
dbSNP: rs139400293
Type: single nucleotide variant
Location: chr11:134178845 (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-ala884val (accessed [today's date]).

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