Is CHCHD10 p.Ser7= (c.21C>T) pathogenic?

CHCHD10 p.Ser7= (c.21C>T) is classified Likely benign in CHCHD10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-11). Very rare (popmax 0.00214%, amr); Associated with Inborn genetic diseases.

How common is CHCHD10 p.Ser7= (c.21C>T) in the general population?

CHCHD10 p.Ser7= (c.21C>T) is very rare (popmax 0.00214%, amr) (gnomAD).

CHCHD10 p.Ser7=

Q: What condition is associated with CHCHD10 p.Ser7= (c.21C>T)?

CHCHD10 p.Ser7= (c.21C>T) is associated with Inborn genetic diseases, lower motor neuron syndrome with late-adult onset, frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (ClinVar).

c.21C>T · rs984321947 · VCV473422

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00214%, amr)

Conditions

Inborn genetic diseases

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 1.3	GERP -2.7, phastCons 0.75
Overall
CADD	8.293	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00214% Admixed American · 1/46,736 alleles

Overall 6.58e-05% 1/1,518,782 alleles · very rare exomes 1/1,366,490 · genomes 0/152,292 · 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.Ser7=
Coding: c.21C>T
MANE Select: NM_213720
dbSNP: rs984321947
Type: single nucleotide variant
Location: chr22:23767854 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.01 · 5 PDB
Residue 7: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lower motor neuron syndrome with late-adult onset frontotemporal dementia and/or amyotrophic lateral sclerosis 2 autosomal dominant mitochondrial myopathy with exercise intolerance

Similar variants

CHCHD10 p.Ser7Asn 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-ser7 (accessed [today's date]).

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