Is CHCHD10 p.Pro19Ser (c.55C>T) pathogenic?

CHCHD10 p.Pro19Ser (c.55C>T) is classified Uncertain significance in CHCHD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-25). AlphaMissense: likely benign (0.0603); Absent from gnomAD v4.1; Associated with lower motor neuron syndrome with late-adult onset.

How common is CHCHD10 p.Pro19Ser (c.55C>T) in the general population?

CHCHD10 p.Pro19Ser (c.55C>T) is absent from gnomAD v4.1 (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.

What do computational predictors say about CHCHD10 p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely benign (score 0.0603) — an in-silico prediction, not a clinical call.

CHCHD10 p.Pro19Ser

Q: What condition is associated with CHCHD10 p.Pro19Ser (c.55C>T)?

CHCHD10 p.Pro19Ser (c.55C>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.55C>T · rs1926950297 · VCV1040911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0603 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,268,302)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lower motor neuron syndrome with late-adult onset

Computational evidence

Protein change
AlphaMissense	0.0603	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -8.01	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 -0.064	GERP 0.65, phastCons 0.66
Regional constraint	o/e 1.03	unconstrained · MANE · 1,864 bp · p 0.66 · regional, not allelic
Overall
CADD	14.96	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

No allele count reported in gnomAD v4.1 (AN 1,268,302). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHCHD10
Protein: p.Pro19Ser
Coding: c.55C>T
MANE Select: NM_213720
dbSNP: rs1926950297
Type: single nucleotide variant
Location: chr22:23767580 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.01 · 5 PDB
Residue 19: 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.Pro19= Likely benign ★ 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-pro19ser (accessed [today's date]).

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