Is PLXNA3 p.Pro366= (c.1098C>T) pathogenic?

PLXNA3 p.Pro366= (c.1098C>T) is classified Likely benign in PLXNA3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-12). Low-frequency (popmax 1.22%, mid); Associated with PLXNA3-related disorder.

What condition is associated with PLXNA3 p.Pro366= (c.1098C>T)?

PLXNA3 p.Pro366= (c.1098C>T) is associated with PLXNA3-related disorder (ClinVar).

How common is PLXNA3 p.Pro366= (c.1098C>T) in the general population?

PLXNA3 p.Pro366= (c.1098C>T) is low-frequency (popmax 1.22%, mid) (gnomAD).

PLXNA3 p.Pro366=

c.1098C>T · rs782760823 · VCV3034709

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, mid)

Conditions

PLXNA3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.16	GERP -0.49, phastCons 0.41
Overall
CADD	6.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.22% Middle Eastern · 53/4,335 alleles

Filtering AF 0.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.866%

Overall 0.0178% 214/1,200,235 alleles · low-frequency exomes 203/1,086,991 · genomes 11/113,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.22%	82
South Asian	0.0603%	1,658
Remaining individualsnot grpmax-eligible	0.04%	2,497
Admixed American	0.0371%	2,697
African / African-American	0.0121%	8,237
European (non-Finnish)	0.0094%	10,635

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: PLXNA3
Protein: p.Pro366=
Coding: c.1098C>T
MANE Select: NM_017514
dbSNP: rs782760823
Type: single nucleotide variant
Location: chrX:154461602 (GRCh38)
Structure: AlphaFold pLDDT 84.77
Residue 366: the sema domain

Full PLXNA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PLXNA3-related disorder

Similar variants

PLXNA3 p.Arg1061His Uncertain significance ★★ ⚠ same condition
PLXNA3 p.Arg519Leu Uncertain significance ★★ ⚠ same condition
PLXNA3 p.Asn1009Thr Uncertain significance ★★ ⚠ same condition
PLXNA3 p.Asp981Ala Uncertain significance ★★ ⚠ same condition
PLXNA3 p.His88Tyr Uncertain significance ★★ ⚠ same condition
PLXNA3 p.Leu339Val Uncertain significance ★★ ⚠ same condition
PLXNA3 p.Leu761Pro Uncertain significance ★★ ⚠ same condition
PLXNA3 p.Ser175Leu 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/plxna3-p-pro366 (accessed [today's date]).

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