Is CHCHD1 p.Leu10Arg (c.29T>G) pathogenic?

CHCHD1 p.Leu10Arg (c.29T>G) is classified Uncertain significance in CHCHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-12). AlphaMissense: likely benign (0.1796); Very rare (popmax 0.000169%, nfe).

How common is CHCHD1 p.Leu10Arg (c.29T>G) in the general population?

CHCHD1 p.Leu10Arg (c.29T>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CHCHD1 p.Leu10Arg (c.29T>G)?

AlphaMissense predicts likely benign (score 0.1796) — an in-silico prediction, not a clinical call.

CHCHD1 p.Leu10Arg

c.29T>G · rs1007822866 · VCV2536280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1796	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -14.73	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 1,108 bp · p 0.7 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,958 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00131% 2/152,222 alleles · very rare

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: CHCHD1
Protein: p.Leu10Arg
Coding: c.29T>G
MANE Select: NM_203298
dbSNP: rs1007822866
Type: single nucleotide variant
Location: chr10:73782104 (GRCh38)
Gene constraint: LOEUF 1.628 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.51 · 64 PDB

Full CHCHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHCHD1 p.Ala83Val Uncertain significance ★ ⚠ same type
CHCHD1 p.Arg32Pro Uncertain significance ★ ⚠ same type
CHCHD1 p.Arg7Trp Uncertain significance ★ ⚠ same type
CHCHD1 p.Arg9Leu Uncertain significance ★ ⚠ same type
CHCHD1 p.Asn24Ser Uncertain significance ★ ⚠ same type
CHCHD1 p.Gln90Arg Uncertain significance ★ ⚠ same type
CHCHD1 p.Glu95Lys Uncertain significance ★ ⚠ same type
CHCHD1 p.Ile70Asn 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/chchd1-p-leu10arg (accessed [today's date]).

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