Is NCAPD2 p.Pro1276= (c.3828T>G) pathogenic?

NCAPD2 p.Pro1276= (c.3828T>G) is classified Benign in NCAPD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele.

NCAPD2 p.Pro1276=

Q: How common is NCAPD2 p.Pro1276= (c.3828T>G) in the general population?

NCAPD2 p.Pro1276= (c.3828T>G) is common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3828T>G · rs61731147 · VCV781060

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -3.3
Overall
CADD	0.707	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.1% African / African-American · 7,543/75,034 alleles

Filtering AF 9.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.79%

Overall 0.53% 8,547/1,613,230 alleles · common exomes 4,250/1,460,906 · genomes 4,297/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.1%	10
Remaining individualsnot grpmax-eligible	0.666%	150
Admixed American	0.642%	156
Middle Eastern	0.462%	216
East Asian	0.0134%	7,477
European (non-Finnish)	0.0133%	7,512
South Asian	0.0132%	7,581

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.Pro1276=
Coding: c.3828T>G
MANE Select: NM_014865
dbSNP: rs61731147
Type: single nucleotide variant
Location: chr12:6529949 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.94

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-pro1276 (accessed [today's date]).

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