Is GJC2 p.Phe320= (c.960C>T) pathogenic?

GJC2 p.Phe320= (c.960C>T) is classified Likely benign in GJC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-03). Very rare (popmax 0.000884%, nfe); Associated with Spastic paraplegia.

What condition is associated with GJC2 p.Phe320= (c.960C>T)?

GJC2 p.Phe320= (c.960C>T) is associated with Spastic paraplegia (ClinVar).

How common is GJC2 p.Phe320= (c.960C>T) in the general population?

GJC2 p.Phe320= (c.960C>T) is very rare (popmax 0.000884%, nfe) (gnomAD).

GJC2 p.Phe320=

c.960C>T · rs1232871344 · VCV2065743

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000884%, nfe)

Conditions

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 -1.2
Overall
CADD	3.154	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000884% European (non-Finnish) · 9/1,018,540 alleles

Filtering AF 0.000416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000301%

Overall 0.000691% 9/1,302,714 alleles · very rare exomes 5/1,155,654 · genomes 4/147,060 · 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: GJC2
Protein: p.Phe320=
Coding: c.960C>T
MANE Select: NM_020435
dbSNP: rs1232871344
Type: single nucleotide variant
Location: chr1:228158718 (GRCh38)
Gene constraint: LOEUF 1.604 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 68.50

Full GJC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GJC2 p.Ala123Ser Uncertain significance ★★ ⚠ same condition
GJC2 p.Ala177Val Uncertain significance ★★ ⚠ same condition
GJC2 p.Ala221Pro Uncertain significance ★★ ⚠ same condition
GJC2 p.Ala340Val Uncertain significance ★★ ⚠ same condition
GJC2 p.Arg115Cys Uncertain significance ★★ ⚠ same condition
GJC2 p.Arg11Gln Uncertain significance ★★ ⚠ same condition
GJC2 p.Arg203His Uncertain significance ★★ ⚠ same condition
GJC2 p.Arg247Cys 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/gjc2-p-phe320 (accessed [today's date]).

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