Is NCAPH p.Val33= (c.99G>T) pathogenic?

NCAPH p.Val33= (c.99G>T) is classified Likely benign in NCAPH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-20). Rare (popmax 0.148%, mid); Associated with NCAPH-related disorder.

What condition is associated with NCAPH p.Val33= (c.99G>T)?

NCAPH p.Val33= (c.99G>T) is associated with NCAPH-related disorder (ClinVar).

How common is NCAPH p.Val33= (c.99G>T) in the general population?

NCAPH p.Val33= (c.99G>T) is rare (popmax 0.148%, mid) (gnomAD).

NCAPH p.Val33=

c.99G>T · rs561015827 · VCV3053109

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Conditions

NCAPH-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.099	GERP -2.8
Overall
CADD	6.995	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,084 alleles

Filtering AF 0.0772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0576%

Overall 0.00607% 98/1,614,108 alleles · rare exomes 91/1,461,886 · genomes 7/152,222 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	676
South Asian	0.0154%	6,507
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)	0.00542%	18,438
Admixed American	0.00333%	30,002

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: NCAPH
Protein: p.Val33=
Coding: c.99G>T
MANE Select: NM_015341
dbSNP: rs561015827
Type: single nucleotide variant
Location: chr2:96341721 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 60.16 · 1 PDB
Residue 33: the 'disordered' region

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

Disease context

NCAPH-related disorder

Similar variants

NCAPH p.Val33Leu Uncertain significance ★ ⚠ same residue
NCAPH c.2091-4C>G Benign same condition
NCAPH c.596-4T>G Likely benign same condition
NCAPH c.-1G>A Likely benign same condition
NCAPH p.Asn333Ser Likely benign same condition
NCAPH p.Asp175= Likely benign same condition
NCAPH p.Ile99Val Benign same condition
NCAPH p.Val340Ile Likely 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/ncaph-p-val33 (accessed [today's date]).

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