Is CHCHD2 p.Pro107Arg (c.320C>G) pathogenic?

CHCHD2 p.Pro107Arg (c.320C>G) is classified Uncertain significance in CHCHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-08). AlphaMissense: likely benign (0.1729); Very rare (popmax 0.000424%, nfe).

How common is CHCHD2 p.Pro107Arg (c.320C>G) in the general population?

CHCHD2 p.Pro107Arg (c.320C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CHCHD2 p.Pro107Arg (c.320C>G)?

AlphaMissense predicts likely benign (score 0.1729) — an in-silico prediction, not a clinical call.

CHCHD2 p.Pro107Arg

c.320C>G · rs1785317244 · VCV1008444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1729	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -8.77	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 0.52	phastCons 0.003
Regional constraint	o/e 0.88	unconstrained · MANE · 4,559 bp · p 0.078 · regional, not allelic
Overall
CADD	13.85	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 0.000424% European (non-Finnish) · 5/1,180,030 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,166 alleles · very rare exomes 5/1,461,872 · genomes 0/152,294 · 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.Pro107Arg
Coding: c.320C>G
MANE Select: NM_016139
dbSNP: rs1785317244
Type: single nucleotide variant
Location: chr7:56102992 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.86 · 2 PDB
Residue 107: the 'disordered' region

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

Similar variants

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
CHCHD2 c.300+159T>G Benign ★★ 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-pro107arg (accessed [today's date]).

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