Is SEMA3B p.Pro152= (c.456C>T) pathogenic?

SEMA3B p.Pro152= (c.456C>T) is classified Likely benign in SEMA3B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-07). Ultra-rare (popmax 0.0111%, amr); Associated with SEMA3B-related disorder.

What condition is associated with SEMA3B p.Pro152= (c.456C>T)?

SEMA3B p.Pro152= (c.456C>T) is associated with SEMA3B-related disorder (ClinVar).

How common is SEMA3B p.Pro152= (c.456C>T) in the general population?

SEMA3B p.Pro152= (c.456C>T) is ultra-rare (popmax 0.0111%, amr) (gnomAD).

SEMA3B p.Pro152=

c.456C>T · VCV3355050

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, amr)

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 -4.9	GERP -3.5
Overall
CADD	5.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% Admixed American · 6/54,106 alleles

Filtering AF 0.00477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00101% 16/1,579,108 alleles · ultra-rare exomes 15/1,427,006 · genomes 1/152,102 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0111%	9,018
African / African-American	0.00135%	74,136
South Asian	0.00116%	86,240
European (non-Finnish)	0.000688%	145,315

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.Pro152=
Coding: c.456C>T
MANE Select: NM_001290060
Type: single nucleotide variant
Location: chr3:50271093 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.84
Residue 152: 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.Pro152Leu Uncertain significance ★ ⚠ same residue
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

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-pro152 (accessed [today's date]).

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