Is SEMA3B p.Pro255= (c.765G>A) pathogenic?

SEMA3B p.Pro255= (c.765G>A) is classified Likely benign in SEMA3B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-03). Very rare (popmax 0.00439%, sas); Associated with SEMA3B-related disorder.

What condition is associated with SEMA3B p.Pro255= (c.765G>A)?

SEMA3B p.Pro255= (c.765G>A) is associated with SEMA3B-related disorder (ClinVar).

How common is SEMA3B p.Pro255= (c.765G>A) in the general population?

SEMA3B p.Pro255= (c.765G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

SEMA3B p.Pro255=

c.765G>A · rs2470772800 · VCV3054514

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

SEMA3B-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 -8	GERP -3.2
Overall
CADD	0.593	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,086 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000479% 7/1,461,434 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
European (non-Finnish)	0.000254%	393,287

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: SEMA3B
Protein: p.Pro255=
Coding: c.765G>A
MANE Select: NM_001290060
dbSNP: rs2470772800
Type: single nucleotide variant
Location: chr3:50273398 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.84
Residue 255: the sema domain

Full SEMA3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SEMA3B-related disorder

Similar variants

SEMA3B p.Ala680Val Likely benign ★★ same condition
SEMA3B p.Arg148Trp Uncertain significance ★ ⚠ same condition
SEMA3B p.Arg371Cys Uncertain significance ★ ⚠ same condition
SEMA3B p.Arg418Ser Uncertain significance ★ ⚠ same condition
SEMA3B p.Arg728Gly Uncertain significance ★ ⚠ same condition
SEMA3B p.Asn221Lys Uncertain significance ★ ⚠ same condition
SEMA3B p.Gly568= Uncertain significance ★ same condition
SEMA3B p.Gly650Asp 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/sema3b-p-pro255 (accessed [today's date]).

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