Is EXOSC2 p.Asp151= (c.453C>T) pathogenic?

EXOSC2 p.Asp151= (c.453C>T) is classified Likely benign in EXOSC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-18). Ultra-rare (popmax 0.0567%, amr).

How common is EXOSC2 p.Asp151= (c.453C>T) in the general population?

EXOSC2 p.Asp151= (c.453C>T) is ultra-rare (popmax 0.0567%, amr) (gnomAD).

EXOSC2 p.Asp151=

c.453C>T · rs370896785 · VCV1154608

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0567%, amr)

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 -9.4	GERP -4.7
Overall
CADD	0.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0567% Admixed American · 34/59,978 alleles

Filtering AF 0.0417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.0102% 165/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0567%	1,764
European (non-Finnish)	0.0101%	9,916
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,009
African / African-American	0.00267%	37,441
East Asian	0.00223%	44,882
South Asian	0.0022%	45,545

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: EXOSC2
Protein: p.Asp151=
Coding: c.453C>T
MANE Select: NM_014285
dbSNP: rs370896785
Type: single nucleotide variant
Location: chr9:130700893 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.25 · 8 PDB
Residue 151: the s1 motif domain; a β-strand

Full EXOSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EXOSC2 p.Asp151Asn Uncertain significance ★ ⚠ same residue
EXOSC2 p.Asp151Val Uncertain significance ★ ⚠ same residue
EXOSC2 p.Arg181Trp Uncertain significance ★★ ⚠ same type
EXOSC2 p.Arg236Trp Uncertain significance ★★ ⚠ same type
EXOSC2 p.Arg238Gln Uncertain significance ★★ ⚠ same type
EXOSC2 p.Arg238Trp Uncertain significance ★★ ⚠ same type
EXOSC2 p.Arg285Cys Uncertain significance ★★ ⚠ same type
EXOSC2 p.Arg62Thr 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/exosc2-p-asp151 (accessed [today's date]).

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