Is NCAPD2 p.Val1267= (c.3801A>G) pathogenic?

NCAPD2 p.Val1267= (c.3801A>G) is classified Benign in NCAPD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-27). Common (popmax 90.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 21, primary, autosomal recessive.

What condition is associated with NCAPD2 p.Val1267= (c.3801A>G)?

NCAPD2 p.Val1267= (c.3801A>G) is associated with microcephaly 21, primary, autosomal recessive (ClinVar).

NCAPD2 p.Val1267=

Q: How common is NCAPD2 p.Val1267= (c.3801A>G) in the general population?

NCAPD2 p.Val1267= (c.3801A>G) is common (popmax 90.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3801A>G · rs1043262 · VCV1321849

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 90.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

microcephaly 21, primary, autosomal recessive

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 1.1	GERP -3.3, phastCons 1
Overall
CADD	1.991	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.2% African / African-American · 67,701/75,042 alleles

Filtering AF 89.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.4%

Overall 72.7% 1,174,097/1,613,992 alleles · common exomes 1,056,491/1,461,776 · genomes 117,606/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	90.2%	1
Admixed American	83.8%	1
Finnishnot grpmax-eligible	75.4%	1
Remaining individualsnot grpmax-eligible	72.8%	1
European (non-Finnish)	71.5%	1
Ashkenazi Jewishnot grpmax-eligible	70.8%	1
Middle Eastern	69%	1
East Asian	68.7%	1
South Asian	68.2%	1
Amishnot grpmax-eligible	61.3%	2

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.Val1267=
Coding: c.3801A>G
MANE Select: NM_014865
dbSNP: rs1043262
Type: single nucleotide variant
Location: chr12:6529922 (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

Disease context

microcephaly 21, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NCAPD2 p.Asn509Ser Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Gln670Ter Uncertain significance ★★ same condition
NCAPD2 c.127+27C>T Benign ★★ same condition
NCAPD2 c.2566+30A>T Benign ★★ same condition
NCAPD2 c.3573-13C>T Benign ★★ same condition
NCAPD2 p.Arg1100= Benign ★★ same condition
NCAPD2 p.Asn1161= Benign ★★ same condition
NCAPD2 p.Gln83Glu 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/ncapd2-p-val1267 (accessed [today's date]).

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