Is RUSC2 p.Asp82= (c.246C>T) pathogenic?

RUSC2 p.Asp82= (c.246C>T) is classified Likely benign in RUSC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0575%, nfe).

How common is RUSC2 p.Asp82= (c.246C>T) in the general population?

RUSC2 p.Asp82= (c.246C>T) is ultra-rare (popmax 0.0575%, nfe) (gnomAD).

RUSC2 p.Asp82=

c.246C>T · rs146775798 · VCV1590746

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0575%, nfe)

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 -1.2	GERP -2.7
Overall
CADD	0.553	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0575% European (non-Finnish) · 675/1,174,382 alleles

Filtering AF 0.0539% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.0506% 811/1,601,818 alleles · ultra-rare exomes 755/1,449,584 · genomes 56/152,234 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.162%	617
European (non-Finnish)grpmax	0.0575%	1,740
Remaining individualsnot grpmax-eligible	0.0387%	2,583
Middle Eastern	0.0166%	6,010
African / African-American	0.00535%	18,694
Ashkenazi Jewishnot grpmax-eligible	0.00352%	28,378
Admixed American	0.0034%	29,379
South Asian	0.00113%	88,190

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RUSC2
Protein: p.Asp82=
Coding: c.246C>T
MANE Select: NM_014806
dbSNP: rs146775798
Type: single nucleotide variant
Location: chr9:35546767 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 45.82 · 1 PDB
Residue 82: the 'disordered' region

Full RUSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RUSC2 p.Arg1393Ter Pathogenic/Likely pathogenic ★★ same type
RUSC2 p.Ala1054Thr Uncertain significance ★★ ⚠ same type
RUSC2 p.Ala1268Thr Uncertain significance ★★ ⚠ same type
RUSC2 p.Ala126Thr Uncertain significance ★★ ⚠ same type
RUSC2 p.Ala319Thr Uncertain significance ★★ ⚠ same type
RUSC2 p.Ala585Thr Uncertain significance ★★ ⚠ same type
RUSC2 p.Ala745Thr Uncertain significance ★★ ⚠ same type
RUSC2 p.Ala886Asp 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/rusc2-p-asp82 (accessed [today's date]).

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