Is SEMA3B p.Pro93= (c.279G>A) pathogenic?

SEMA3B p.Pro93= (c.279G>A) is classified Likely benign in SEMA3B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-07-13). Ultra-rare (popmax 0.0767%, amr); Associated with SEMA3B-related disorder.

What condition is associated with SEMA3B p.Pro93= (c.279G>A)?

SEMA3B p.Pro93= (c.279G>A) is associated with SEMA3B-related disorder (ClinVar).

How common is SEMA3B p.Pro93= (c.279G>A) in the general population?

SEMA3B p.Pro93= (c.279G>A) is ultra-rare (popmax 0.0767%, amr) (gnomAD).

SEMA3B p.Pro93=

c.279G>A · rs782183921 · VCV3048220

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0767%, amr)

Conditions

SEMA3B-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 -2.4	GERP -3.3
Overall
CADD	9.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0767% Admixed American · 46/59,996 alleles

Filtering AF 0.0591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0528%

Overall 0.00583% 94/1,613,602 alleles · ultra-rare exomes 88/1,461,424 · genomes 6/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0767%	1,304
Middle Eastern	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.00961%	10,409
South Asian	0.00659%	15,181
African / African-American	0.00267%	37,462
European (non-Finnish)	0.00263%	38,060
East Asian	0.00223%	44,896

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.Pro93=
Coding: c.279G>A
MANE Select: NM_001290060
dbSNP: rs782183921
Type: single nucleotide variant
Location: chr3:50270444 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.84
Residue 93: 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-pro93 (accessed [today's date]).

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