Is CHCHD7 p.Ser23= (c.69C>T) pathogenic?

CHCHD7 p.Ser23= (c.69C>T) is classified Likely benign in CHCHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). Ultra-rare (popmax 0.0105%, nfe).

How common is CHCHD7 p.Ser23= (c.69C>T) in the general population?

CHCHD7 p.Ser23= (c.69C>T) is ultra-rare (popmax 0.0105%, nfe) (gnomAD).

CHCHD7 p.Ser23=

c.69C>T · VCV3266823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.153	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -2, phastCons 0.65
Overall
CADD	5.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% European (non-Finnish) · 124/1,179,770 alleles

Filtering AF 0.00891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00842%

Overall 0.00812% 131/1,613,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0105%	9,514
Remaining individualsnot grpmax-eligible	0.0064%	15,625
Admixed American	0.00167%	60,024
African / African-American	0.00133%	75,024
South Asian	0.0011%	91,078

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: CHCHD7
Protein: p.Ser23=
Coding: c.69C>T
MANE Select: NM_001011671
Type: single nucleotide variant
Location: chr8:56216447 (GRCh38)
Gene constraint: LOEUF 1.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.77 · 1 PDB
Residue 23: the chch domain; a disulfide bond; an α-helix

Full CHCHD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHCHD7 c.-17+1017A>G Uncertain significance ★ same type
CHCHD7 c.-17+1036C>G Uncertain significance ★ same type
CHCHD7 p.Arg36Gly Uncertain significance ★ ⚠ same type
CHCHD7 p.Asp21His Uncertain significance ★ same type
CHCHD7 p.Asp28Tyr Uncertain significance ★ ⚠ same type
CHCHD7 p.Ile54Phe Uncertain significance ★ ⚠ same type
CHCHD7 p.Leu27Val Uncertain significance ★ ⚠ same type
CHCHD7 p.Leu42Phe 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/chchd7-p-ser23 (accessed [today's date]).

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