Is CHCHD2 p.Arg51Pro (c.152G>C) pathogenic?

CHCHD2 p.Arg51Pro (c.152G>C) is classified Uncertain significance in CHCHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: ambiguous (0.4842); Absent from gnomAD v4.1.

How common is CHCHD2 p.Arg51Pro (c.152G>C) in the general population?

CHCHD2 p.Arg51Pro (c.152G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHCHD2 p.Arg51Pro (c.152G>C)?

AlphaMissense predicts ambiguous (score 0.4842) — an in-silico prediction, not a clinical call.

CHCHD2 p.Arg51Pro

c.152G>C · rs1304695607 · VCV2548754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4842	ambiguous
REVEL	0.153	moderately benign-leaning
SaProt	LLR -7.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	phastCons 0.005
Regional constraint	o/e 0.88	unconstrained · MANE · 4,559 bp · p 0.078 · regional, not allelic
Overall
CADD	22.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHCHD2
Protein: p.Arg51Pro
Coding: c.152G>C
MANE Select: NM_016139
dbSNP: rs1304695607
Type: single nucleotide variant
Location: chr7:56104374 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.86 · 2 PDB

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

Similar variants

CHCHD2 p.Arg51Gln Uncertain significance ★★ ⚠ same residue
CHCHD2 p.Arg51Trp Conflicting classifications of pathogenicity ★ ⚠ 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.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-arg51pro (accessed [today's date]).

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