Is SEMA6B p.Pro548= (c.1644C>T) pathogenic?

SEMA6B p.Pro548= (c.1644C>T) is classified Likely benign in SEMA6B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-07). Rare (popmax 0.403%, afr); Associated with SEMA6B-related disorder.

What condition is associated with SEMA6B p.Pro548= (c.1644C>T)?

SEMA6B p.Pro548= (c.1644C>T) is associated with SEMA6B-related disorder (ClinVar).

How common is SEMA6B p.Pro548= (c.1644C>T) in the general population?

SEMA6B p.Pro548= (c.1644C>T) is rare (popmax 0.403%, afr) (gnomAD).

SEMA6B p.Pro548=

c.1644C>T · rs145677334 · VCV3038213

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.403%, afr)

Conditions

SEMA6B-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 -14	GERP -3.2
Overall
CADD	2.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.403% African / African-American · 299/74,142 alleles

Filtering AF 0.366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.351%

Overall 0.022% 348/1,579,914 alleles · rare exomes 180/1,427,682 · genomes 168/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.403%	248
Middle Eastern	0.133%	749
Remaining individualsnot grpmax-eligible	0.0262%	3,813
Admixed American	0.0251%	3,988
South Asian	0.00231%	43,336
European (non-Finnish)	0.000774%	129,139

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.Pro548=
Coding: c.1644C>T
MANE Select: NM_032108
dbSNP: rs145677334
Type: single nucleotide variant
Location: chr19:4546427 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81

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

Disease context

SEMA6B-related disorder

Similar variants

SEMA6B p.Ala181Pro Uncertain significance ★ ⚠ same condition
SEMA6B p.Thr826Met Uncertain significance ★ ⚠ same condition
SEMA6B p.Asn597Asp Uncertain significance ⚠ same condition
SEMA6B p.Gly124Ala Uncertain significance ⚠ same condition
SEMA6B p.Ala380= Likely benign same condition
SEMA6B p.Ala611= Likely benign same condition
SEMA6B p.Ala641= Likely benign same condition
SEMA6B p.Gly705= 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-pro548 (accessed [today's date]).

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