Is CHCHD10 p.Val57= (c.171G>A) pathogenic?

CHCHD10 p.Val57= (c.171G>A) is classified Likely benign in CHCHD10 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-05). Ultra-rare (popmax 0.0183%, nfe); Associated with Inborn genetic diseases.

How common is CHCHD10 p.Val57= (c.171G>A) in the general population?

CHCHD10 p.Val57= (c.171G>A) is ultra-rare (popmax 0.0183%, nfe) (gnomAD).

CHCHD10 p.Val57=

Q: What condition is associated with CHCHD10 p.Val57= (c.171G>A)?

CHCHD10 p.Val57= (c.171G>A) is associated with Inborn genetic diseases, lower motor neuron syndrome with late-adult onset, frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (ClinVar).

c.171G>A · rs780298646 · VCV506461

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.119	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.057, phastCons 1
Overall
CADD	13.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% European (non-Finnish) · 215/1,173,234 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.014% 224/1,596,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0183%	5,457
Admixed American	0.0102%	9,779
Remaining individualsnot grpmax-eligible	0.00325%	30,801
African / African-American	0.00135%	73,962

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.Val57=
Coding: c.171G>A
MANE Select: NM_213720
dbSNP: rs780298646
Type: single nucleotide variant
Location: chr22:23767464 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.01 · 5 PDB
Residue 57: a β-strand

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.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
CHCHD10 p.Arg11Trp 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-val57 (accessed [today's date]).

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