Is PLXNA3 p.Ala1237= (c.3711C>T) pathogenic?

PLXNA3 p.Ala1237= (c.3711C>T) is classified Likely benign in PLXNA3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-18). Ultra-rare (popmax 0.0211%, sas); Associated with PLXNA3-related disorder.

What condition is associated with PLXNA3 p.Ala1237= (c.3711C>T)?

PLXNA3 p.Ala1237= (c.3711C>T) is associated with PLXNA3-related disorder (ClinVar).

How common is PLXNA3 p.Ala1237= (c.3711C>T) in the general population?

PLXNA3 p.Ala1237= (c.3711C>T) is ultra-rare (popmax 0.0211%, sas) (gnomAD).

PLXNA3 p.Ala1237=

c.3711C>T · VCV3352453

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, sas)

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 -20	GERP -3.4
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0211% South Asian · 12/56,792 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00955%

Overall 0.00439% 53/1,207,328 alleles · ultra-rare exomes 51/1,095,493 · genomes 2/111,835 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0211%	4,733
Remaining individualsnot grpmax-eligible	0.00842%	11,883
European (non-Finnish)	0.00391%	25,544
African / African-American	0.0035%	28,588

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.Ala1237=
Coding: c.3711C>T
MANE Select: NM_017514
Type: single nucleotide variant
Location: chrX:154467892 (GRCh38)
Structure: AlphaFold pLDDT 84.77

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

Disease context

PLXNA3-related disorder

Similar variants

PLXNA3 p.Ala1237Val Uncertain significance ★ ⚠ same residue
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

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-ala1237 (accessed [today's date]).

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