Is ZFR p.Pro220= (c.660A>G) pathogenic?

ZFR p.Pro220= (c.660A>G) is classified Likely benign in ZFR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). Absent from gnomAD v4.1; Associated with Pure or complex autosomal recessive spastic paraplegia.

What condition is associated with ZFR p.Pro220= (c.660A>G)?

ZFR p.Pro220= (c.660A>G) is associated with Pure or complex autosomal recessive spastic paraplegia (ClinVar).

How common is ZFR p.Pro220= (c.660A>G) in the general population?

ZFR p.Pro220= (c.660A>G) is absent from gnomAD v4.1 (gnomAD).

ZFR p.Pro220=

c.660A>G · rs2478448396 · VCV2091187

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Pure or complex autosomal recessive spastic paraplegia

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 0.31	GERP 0.36, phastCons 1
Overall
CADD	9.947	PHRED · no single calibrated threshold — expert panels disagree

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: ZFR
Protein: p.Pro220=
Coding: c.660A>G
MANE Select: NM_016107
dbSNP: rs2478448396
Type: single nucleotide variant
Location: chr5:32415093 (GRCh38)
Gene constraint: LOEUF 0.219 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.11

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

Disease context

Pure or complex autosomal recessive spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ZFR p.Ala833Gly Uncertain significance ★★ ⚠ same condition
ZFR p.Arg669Lys Uncertain significance ★★ ⚠ same condition
ZFR p.Arg681His Uncertain significance ★★ ⚠ same condition
ZFR p.Arg915Lys Uncertain significance ★★ ⚠ same condition
ZFR p.Asn595Ser Uncertain significance ★★ ⚠ same condition
ZFR p.Ile1026Val Uncertain significance ★★ ⚠ same condition
ZFR p.Lys830Glu Uncertain significance ★★ ⚠ same condition
ZFR p.Met1038Ile Uncertain significance ★★ ⚠ same condition

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/zfr-p-pro220 (accessed [today's date]).

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