Is CHCHD2 p.Thr61= (c.183C>T) pathogenic?

CHCHD2 p.Thr61= (c.183C>T) is classified Likely benign in CHCHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-17). Very rare (popmax 8.48e-05%, nfe).

How common is CHCHD2 p.Thr61= (c.183C>T) in the general population?

CHCHD2 p.Thr61= (c.183C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CHCHD2 p.Thr61=

c.183C>T · rs893913404 · VCV2415618

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 4.4	phastCons 1
Overall
CADD	10.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,572 alleles

Overall 6.2e-05% 1/1,613,434 alleles · very rare exomes 1/1,461,126 · genomes 0/152,308 · 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: CHCHD2
Protein: p.Thr61=
Coding: c.183C>T
MANE Select: NM_016139
dbSNP: rs893913404
Type: single nucleotide variant
Location: chr7:56104343 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.86 · 2 PDB
Residue 61: a UniProt-annotated variant site (in park22; does not affect subcellular location); a β-strand

Full CHCHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHCHD2 p.Thr61Ile Pathogenic ★ same residue
CHCHD2 c.446-9T>A Uncertain significance ★★ same type
CHCHD2 p.Ala32Thr Uncertain significance ★★ ⚠ same type
CHCHD2 p.Ala60Val Uncertain significance ★★ ⚠ same type
CHCHD2 p.Arg51Gln Uncertain significance ★★ ⚠ same type
CHCHD2 p.Ile131Val Uncertain significance ★★ ⚠ same type
CHCHD2 p.Pro34Leu Uncertain significance ★★ ⚠ same type
CHCHD2 p.Pro39Thr Uncertain significance ★★ ⚠ same type

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/chchd2-p-thr61 (accessed [today's date]).

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