Is CHCHD10 p.Ala92= (c.276T>G) pathogenic?

CHCHD10 p.Ala92= (c.276T>G) is classified Likely benign in CHCHD10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-10). Ultra-rare (popmax 0.0569%, nfe); Associated with CHCHD10-related disorder.

What condition is associated with CHCHD10 p.Ala92= (c.276T>G)?

CHCHD10 p.Ala92= (c.276T>G) is associated with CHCHD10-related disorder (ClinVar).

How common is CHCHD10 p.Ala92= (c.276T>G) in the general population?

CHCHD10 p.Ala92= (c.276T>G) is ultra-rare (popmax 0.0569%, nfe) (gnomAD).

CHCHD10 p.Ala92=

c.276T>G · rs1252496774 · VCV3041658

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0569%, nfe)

Conditions

CHCHD10-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.078	moderately benign-leaning
Splicing
SpliceAI	Δ0.45	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.28	GERP -0.78
Overall
CADD	2.753	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0569% European (non-Finnish) · 432/759,724 alleles

Filtering AF 0.0524% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0507%

Overall 0.0445% 477/1,071,644 alleles · ultra-rare exomes 477/949,424 · genomes 0/122,220 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0569%	1,759
Remaining individualsnot grpmax-eligible	0.0553%	1,808
South Asian	0.0144%	6,955
African / African-American	0.0139%	7,204
Ashkenazi Jewishnot grpmax-eligible	0.0134%	7,459
East Asian	0.0034%	29,410

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.Ala92=
Coding: c.276T>G
MANE Select: NM_213720
dbSNP: rs1252496774
Type: single nucleotide variant
Location: chr22:23766261 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.01 · 5 PDB
Residue 92: the 'disordered' region

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

Disease context

CHCHD10-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHCHD10 p.Ala92Pro Benign/Likely benign ★★ same residue
CHCHD10 p.Ala92Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CHCHD10 p.Ser59Leu Pathogenic/Likely pathogenic ★★ same condition
CHCHD10 p.Pro36Ser Uncertain significance ★★ ⚠ same condition
CHCHD10 c.41+7G>A Benign/Likely benign ★★ same condition
CHCHD10 c.42-5C>G Conflicting classifications of pathogenicity ★ same condition
CHCHD10 p.Ala92fs Uncertain significance ★ same residue
CHCHD10 p.Ser113Cys 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-ala92 (accessed [today's date]).

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