Is CHPF2 p.Pro82= (c.246C>T) pathogenic?

CHPF2 p.Pro82= (c.246C>T) is classified Likely benign in CHPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Very rare (popmax 8.54e-05%, nfe).

How common is CHPF2 p.Pro82= (c.246C>T) in the general population?

CHPF2 p.Pro82= (c.246C>T) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

CHPF2 p.Pro82=

c.246C>T · rs1374373933 · VCV2658185

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.54e-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 -0.091	GERP -3, phastCons 0.54
Overall
CADD	9.393	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,171,340 alleles

Overall 0.000657% 1/152,206 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: CHPF2
Protein: p.Pro82=
Coding: c.246C>T
MANE Select: NM_019015
dbSNP: rs1374373933
Type: single nucleotide variant
Location: chr7:151234257 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86

Full CHPF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHPF2 p.Pro82Ser Uncertain significance ★ ⚠ same residue
CHPF2 p.Arg254His Benign ★★ same type
CHPF2 p.Arg460Gln Benign/Likely benign ★★ same type
CHPF2 p.Ala189Ser Uncertain significance ★ ⚠ same type
CHPF2 p.Ala216Thr Uncertain significance ★ ⚠ same type
CHPF2 p.Ala220Thr Uncertain significance ★ ⚠ same type
CHPF2 p.Ala352Gly Uncertain significance ★ ⚠ same type
CHPF2 p.Ala406Val 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/chpf2-p-pro82 (accessed [today's date]).

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