Is EXOSC3 p.Asp41= (c.123C>T) pathogenic?

EXOSC3 p.Asp41= (c.123C>T) is classified Likely benign in EXOSC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.117%, afr); Associated with pontocerebellar hypoplasia type 1B.

What condition is associated with EXOSC3 p.Asp41= (c.123C>T)?

EXOSC3 p.Asp41= (c.123C>T) is associated with pontocerebellar hypoplasia type 1B (ClinVar).

How common is EXOSC3 p.Asp41= (c.123C>T) in the general population?

EXOSC3 p.Asp41= (c.123C>T) is rare (popmax 0.117%, afr) (gnomAD).

EXOSC3 p.Asp41=

c.123C>T · rs147510873 · VCV705030

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.117%, afr)

Conditions

pontocerebellar hypoplasia type 1B

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 0.76	GERP -2.8, phastCons 0.2
Overall
CADD	10.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.117% African / African-American · 88/74,986 alleles

Filtering AF 0.0975% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0902%

Overall 0.00783% 126/1,609,972 alleles · rare exomes 63/1,457,634 · genomes 63/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.117%	852
Admixed American	0.0353%	2,836
Remaining individualsnot grpmax-eligible	0.0193%	5,191
Middle Eastern	0.0165%	6,054
East Asian	0.00224%	44,664
European (non-Finnish)	0.000255%	392,779

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: EXOSC3
Protein: p.Asp41=
Coding: c.123C>T
MANE Select: NM_016042
dbSNP: rs147510873
Type: single nucleotide variant
Location: chr9:37784922 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.26 · 8 PDB

Full EXOSC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EXOSC3 p.Arg186Ter Pathogenic/Likely pathogenic ★★ same condition
EXOSC3 p.Asp132Ala Pathogenic ★★ same condition
EXOSC3 p.Gly191Asp Likely pathogenic ★★ same condition
EXOSC3 p.Gly31Ala Pathogenic/Likely pathogenic ★★ same condition
EXOSC3 p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
EXOSC3 p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
EXOSC3 p.Val80Phe Pathogenic/Likely pathogenic ★★ same condition
EXOSC3 p.Ala139Pro Uncertain significance ★★ ⚠ same condition

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/exosc3-p-asp41 (accessed [today's date]).

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