Is NACA p.Thr1010= (c.3030A>G) pathogenic?

NACA p.Thr1010= (c.3030A>G) is classified Likely benign in NACA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Very rare (popmax 0.00516%, sas).

How common is NACA p.Thr1010= (c.3030A>G) in the general population?

NACA p.Thr1010= (c.3030A>G) is very rare (popmax 0.00516%, sas) (gnomAD).

NACA p.Thr1010=

c.3030A>G · VCV4681416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00516%, sas)

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 -5.1	GERP -1.8
Overall
CADD	0.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00516% South Asian · 2/38,754 alleles

Filtering AF 0.000855% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00032%

Overall 0.0002% 2/1,001,994 alleles · very rare

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.Thr1010=
Coding: c.3030A>G
MANE Select: NM_001365896
Type: single nucleotide variant
Location: chr12:56718500 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 38.15 · 26 PDB
Residue 1010: 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-thr1010 (accessed [today's date]).

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