Is CHCHD10 p.Pro27Ser (c.79C>T) pathogenic?

CHCHD10 p.Pro27Ser (c.79C>T) is classified Uncertain significance in CHCHD10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-18). AlphaMissense: likely benign (0.0706); Ultra-rare (popmax 0.0121%, eas); Associated with Inborn genetic diseases.

How common is CHCHD10 p.Pro27Ser (c.79C>T) in the general population?

CHCHD10 p.Pro27Ser (c.79C>T) is ultra-rare (popmax 0.0121%, eas) (gnomAD).

What do computational predictors say about CHCHD10 p.Pro27Ser (c.79C>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

CHCHD10 p.Pro27Ser

Q: What condition is associated with CHCHD10 p.Pro27Ser (c.79C>T)?

CHCHD10 p.Pro27Ser (c.79C>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.79C>T · rs1297070374 · VCV1397008

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.76	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 6.1	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,864 bp · p 0.66 · regional, not allelic
Overall
CADD	19.88	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

Grpmax group 0.0121% East Asian · 4/33,176 alleles

Filtering AF 0.00411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00239%

Overall 0.000575% 8/1,391,974 alleles · ultra-rare exomes 4/1,239,736 · genomes 4/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0121%	8,294
Remaining individualsnot grpmax-eligible	0.00378%	26,475
South Asian	0.00155%	64,442
European (non-Finnish)	9.29e-05%	1,076,760

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.Pro27Ser
Coding: c.79C>T
MANE Select: NM_213720
dbSNP: rs1297070374
Type: single nucleotide variant
Location: chr22:23767556 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.01 · 5 PDB
Residue 27: 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.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-pro27ser (accessed [today's date]).

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