Is NCAPD2 p.Ser188= (c.564A>C) pathogenic?

NCAPD2 p.Ser188= (c.564A>C) is classified Benign in NCAPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Low-frequency (popmax 2.51%, mid).

How common is NCAPD2 p.Ser188= (c.564A>C) in the general population?

NCAPD2 p.Ser188= (c.564A>C) is low-frequency (popmax 2.51%, mid) (gnomAD).

NCAPD2 p.Ser188=

c.564A>C · rs61753198 · VCV1879223

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.51%, mid)

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 -0.44	GERP -1.7
Overall
CADD	6.323	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.51% Middle Eastern · 152/6,062 alleles

Filtering AF 2.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.06%

Overall 1.04% 16,767/1,614,136 alleles · low-frequency exomes 15,085/1,461,850 · genomes 1,682/152,286 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	6.22%	16
Amishnot grpmax-eligible	5.81%	17
Finnishnot grpmax-eligible	4.13%	24
Middle Easterngrpmax	2.51%	40
Remaining individualsnot grpmax-eligible	1.27%	79
European (non-Finnish)	0.898%	111
Admixed American	0.585%	171
South Asian	0.225%	444
African / African-American	0.173%	577
East Asian	0.00223%	44,888

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NCAPD2
Protein: p.Ser188=
Coding: c.564A>C
MANE Select: NM_014865
dbSNP: rs61753198
Type: single nucleotide variant
Location: chr12:6511229 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.94
Residue 188: the 'interactions with smc2 and smc4' region

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

Similar variants

NCAPD2 c.2735-6C>T Uncertain significance ★★ same type
NCAPD2 p.Ala43Gly Uncertain significance ★★ ⚠ same type
NCAPD2 p.Arg1397His Uncertain significance ★★ ⚠ same type
NCAPD2 p.Arg677His Uncertain significance ★★ ⚠ same type
NCAPD2 p.Arg952Cys Uncertain significance ★★ ⚠ same type
NCAPD2 p.Asn509Ser Uncertain significance ★★ ⚠ same type
NCAPD2 p.Asn598Ile Uncertain significance ★★ ⚠ same type
NCAPD2 p.Gln670Ter 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/ncapd2-p-ser188 (accessed [today's date]).

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