Is SEMA6B p.Leu730= (c.2190G>A) pathogenic?

SEMA6B p.Leu730= (c.2190G>A) is classified Likely benign in SEMA6B (ClinVar, Single submitter, 2 submitters; last evaluated 2023-03-08). Rare (popmax 0.242%, afr); Associated with inherited retinal dystrophy.

What condition is associated with SEMA6B p.Leu730= (c.2190G>A)?

SEMA6B p.Leu730= (c.2190G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is SEMA6B p.Leu730= (c.2190G>A) in the general population?

SEMA6B p.Leu730= (c.2190G>A) is rare (popmax 0.242%, afr) (gnomAD).

SEMA6B p.Leu730=

c.2190G>A · VCV3249301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.242%, afr)

Conditions

inherited retinal dystrophy

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 0.025	GERP -0.27, phastCons 0.51
Overall
CADD	2.805	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.242% African / African-American · 153/63,126 alleles

Filtering AF 0.211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.199%

Overall 0.015% 186/1,240,102 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.242%	413
Middle Eastern	0.0627%	1,596
Remaining individualsnot grpmax-eligible	0.0464%	2,156
Admixed American	0.0301%	3,322
South Asian	0.0093%	10,755

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: SEMA6B
Protein: p.Leu730=
Coding: c.2190G>A
MANE Select: NM_032108
Type: single nucleotide variant
Location: chr19:4544078 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 730: the 'disordered' region

Full SEMA6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEMA6B p.Arg781Leu Benign/Likely benign ★★ same condition
SEMA6B p.Ala865Gly Uncertain significance ★ ⚠ same condition
SEMA6B p.Arg482Trp Uncertain significance ★ ⚠ same condition
SEMA6B p.Ala346Asp Likely benign ★ same condition
SEMA6B p.Arg374Trp Likely benign ★ same condition
SEMA6B p.Arg497Gln Likely benign ★ same condition
SEMA6B p.Arg520Gln Likely benign ★ same condition
SEMA6B p.Pro364Leu Likely benign ★ 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/sema6b-p-leu730 (accessed [today's date]).

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