Is NCAPD2 p.Arg519Ser (c.1555C>A) pathogenic?

NCAPD2 p.Arg519Ser (c.1555C>A) is classified Uncertain significance in NCAPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: likely benign (0.267); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NCAPD2 p.Arg519Ser (c.1555C>A)?

NCAPD2 p.Arg519Ser (c.1555C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NCAPD2 p.Arg519Ser (c.1555C>A) in the general population?

NCAPD2 p.Arg519Ser (c.1555C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NCAPD2 p.Arg519Ser (c.1555C>A)?

AlphaMissense predicts likely benign (score 0.267) — an in-silico prediction, not a clinical call.

NCAPD2 p.Arg519Ser

c.1555C>A · VCV3403190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.267 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.267	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.7, phastCons 0.046
Regional constraint	o/e 0.89	unconstrained · MANE · 36 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	20.4	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

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: NCAPD2
Protein: p.Arg519Ser
Coding: c.1555C>A
MANE Select: NM_014865
Type: single nucleotide variant
Location: chr12:6517925 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.94
Residue 519: the 'interactions with smc2 and smc4' region

Full NCAPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NCAPD2 p.Arg519His Uncertain significance ★ ⚠ same residue
NCAPD2 c.2735-6C>T Uncertain significance ★★ same condition
NCAPD2 p.Ala43Gly Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Arg1397His Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Arg677His Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Asn598Ile Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Glu1178Lys Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Glu883Lys Uncertain significance ★★ ⚠ 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/ncapd2-p-arg519ser (accessed [today's date]).

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