Is NACA p.Pro1134= (c.3402C>T) pathogenic?

NACA p.Pro1134= (c.3402C>T) is classified Likely benign in NACA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Very rare (popmax 0.00806%, afr).

How common is NACA p.Pro1134= (c.3402C>T) in the general population?

NACA p.Pro1134= (c.3402C>T) is very rare (popmax 0.00806%, afr) (gnomAD).

NACA p.Pro1134=

c.3402C>T · VCV3257641

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00806%, afr)

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 -20	GERP -2.1
Overall
CADD	0.706	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00806% African / African-American · 3/37,242 alleles

Filtering AF 0.00214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00153% 13/848,082 alleles · very rare exomes 7/796,566 · genomes 6/51,516 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00806%	12,414
Admixed American	0.00696%	14,374
European (non-Finnish)	0.00126%	79,094

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: NACA
Protein: p.Pro1134=
Coding: c.3402C>T
MANE Select: NM_001365896
Type: single nucleotide variant
Location: chr12:56718128 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 38.15 · 26 PDB
Residue 1134: the 'disordered' region

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

Similar variants

NACA p.Ala242= Benign ★★ same type
NACA p.Phe405Ser Benign ★★ same type
NACA p.Pro1772Ser Benign ★★ same type
NACA p.Pro490Arg Benign ★★ same type
NACA p.Ala152Val Uncertain significance ★ ⚠ same type
NACA p.Ala1803Pro Uncertain significance ★ ⚠ same type
NACA p.Ala1833Val Uncertain significance ★ ⚠ same type
NACA p.Ala1868Val 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/naca-p-pro1134 (accessed [today's date]).

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