Is EXOSC3 p.Ala5= (c.15G>T) pathogenic?

EXOSC3 p.Ala5= (c.15G>T) is classified Likely benign in EXOSC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). Very rare (popmax 0.000171%, nfe); Associated with pontocerebellar hypoplasia type 1B.

What condition is associated with EXOSC3 p.Ala5= (c.15G>T)?

EXOSC3 p.Ala5= (c.15G>T) is associated with pontocerebellar hypoplasia type 1B (ClinVar).

How common is EXOSC3 p.Ala5= (c.15G>T) in the general population?

EXOSC3 p.Ala5= (c.15G>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

EXOSC3 p.Ala5=

c.15G>T · rs774976928 · VCV2801797

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

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 -2.7	GERP -3.1
Overall
CADD	4.433	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,170,902 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,598,924 alleles · very rare exomes 2/1,446,556 · genomes 0/152,368 · joint denominator

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.Ala5=
Coding: c.15G>T
MANE Select: NM_016042
dbSNP: rs774976928
Type: single nucleotide variant
Location: chr9:37785030 (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.Ala5Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
EXOSC3 p.Ala5Thr Uncertain significance ★ ⚠ same residue
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

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-ala5 (accessed [today's date]).

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