Is RUSC2 p.Gly1237Asp (c.3710G>A) pathogenic?

RUSC2 p.Gly1237Asp (c.3710G>A) is classified Uncertain significance in RUSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.1283); Very rare (popmax 0.00892%, eas).

How common is RUSC2 p.Gly1237Asp (c.3710G>A) in the general population?

RUSC2 p.Gly1237Asp (c.3710G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about RUSC2 p.Gly1237Asp (c.3710G>A)?

AlphaMissense predicts likely benign (score 0.1283) — an in-silico prediction, not a clinical call.

RUSC2 p.Gly1237Asp

c.3710G>A · rs752602289 · VCV2553797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1283 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1283	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.65, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 3.4e-06 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,832 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,611,962 alleles · very rare exomes 4/1,459,826 · genomes 1/152,136 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,208
Remaining individualsnot grpmax-eligible	0.0016%	62,398

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.Gly1237Asp
Coding: c.3710G>A
MANE Select: NM_014806
dbSNP: rs752602289
Type: single nucleotide variant
Location: chr9:35560350 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 45.82 · 1 PDB
Residue 1237: the 'disordered' region; a UniProt-annotated variant site (in mrt61; uncertain significance)

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-gly1237asp (accessed [today's date]).

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