Is CHCHD10 p.Pro16= (c.48A>T) pathogenic?

CHCHD10 p.Pro16= (c.48A>T) is classified Likely benign in CHCHD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). Very rare (popmax 0.00023%, nfe); Associated with lower motor neuron syndrome with late-adult onset.

How common is CHCHD10 p.Pro16= (c.48A>T) in the general population?

CHCHD10 p.Pro16= (c.48A>T) is very rare (popmax 0.00023%, nfe) (gnomAD).

How is Lower motor neuron syndrome with late-adult onset inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CHCHD10 p.Pro16=

Q: What condition is associated with CHCHD10 p.Pro16= (c.48A>T)?

CHCHD10 p.Pro16= (c.48A>T) is associated with lower motor neuron syndrome with late-adult onset, frontotemporal dementia and/or amyotrophic lateral sclerosis 2, autosomal dominant mitochondrial myopathy with exercise intolerance (ClinVar).

c.48A>T · rs179468 · VCV2187552

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00023%, nfe)

Conditions

lower motor neuron syndrome with late-adult onset

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 -0.92	GERP -4
Overall
CADD	5.629	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00023% European (non-Finnish) · 2/867,992 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000175% 2/1,141,976 alleles · very rare exomes 1/990,164 · genomes 1/151,812 · 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: CHCHD10
Protein: p.Pro16=
Coding: c.48A>T
MANE Select: NM_213720
dbSNP: rs179468
Type: single nucleotide variant
Location: chr22:23767587 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.01 · 5 PDB
Residue 16: the 'disordered' region

Full CHCHD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lower motor neuron syndrome with late-adult onset — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: frontotemporal dementia and/or amyotrophic lateral sclerosis 2 autosomal dominant mitochondrial myopathy with exercise intolerance

For Lower motor neuron syndrome with late-adult onset (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

CHCHD10 p.Pro16Ser Uncertain significance ★★ ⚠ same residue
CHCHD10 p.Ser59Leu Pathogenic/Likely pathogenic ★★ same condition
CHCHD10 c.262-3C>G Uncertain significance ★★ same condition
CHCHD10 c.409+1G>A Uncertain significance ★★ same condition
CHCHD10 p.Ala31Val Uncertain significance ★★ ⚠ same condition
CHCHD10 p.Ala35Thr Uncertain significance ★★ ⚠ same condition
CHCHD10 p.Ala49Val Uncertain significance ★★ ⚠ same condition
CHCHD10 p.Arg11Gly 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/chchd10-p-pro16 (accessed [today's date]).

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