Is SEMA3A p.Val243= (c.729A>G) pathogenic?

SEMA3A p.Val243= (c.729A>G) is classified Likely benign in SEMA3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-29). Very rare (popmax 0.00893%, eas); Associated with SEMA3A-related disorder.

What condition is associated with SEMA3A p.Val243= (c.729A>G)?

SEMA3A p.Val243= (c.729A>G) is associated with SEMA3A-related disorder (ClinVar).

How common is SEMA3A p.Val243= (c.729A>G) in the general population?

SEMA3A p.Val243= (c.729A>G) is very rare (popmax 0.00893%, eas) (gnomAD).

SEMA3A p.Val243=

c.729A>G · VCV3355453

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Conditions

SEMA3A-related disorder

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 -3	GERP -5.3
Overall
CADD	2.298	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,782 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000496% 8/1,613,164 alleles · very rare exomes 8/1,460,858 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,196
European (non-Finnish)	0.000339%	294,840

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: SEMA3A
Protein: p.Val243=
Coding: c.729A>G
MANE Select: NM_006080
Type: single nucleotide variant
Location: chr7:84014290 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 84.50
Residue 243: the sema domain

Full SEMA3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SEMA3A-related disorder

Similar variants

SEMA3A p.Val243Ile Uncertain significance ★ ⚠ same residue
SEMA3A p.Ala523Val Uncertain significance ★★ ⚠ same condition
SEMA3A p.Arg617Ter Uncertain significance ★★ same condition
SEMA3A p.Ile421Met Uncertain significance ★★ ⚠ same condition
SEMA3A p.Pro374His Uncertain significance ★★ ⚠ same condition
SEMA3A c.1860+1G>A Pathogenic ★ same condition
SEMA3A p.Glu589Gln Uncertain significance ★ ⚠ same condition
SEMA3A p.Trp3Cys 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/sema3a-p-val243 (accessed [today's date]).

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