Is SECISBP2 p.Ser46Phe (c.137C>T) pathogenic?

SECISBP2 p.Ser46Phe (c.137C>T) is classified Uncertain significance in SECISBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0923); Ultra-rare (popmax 0.0183%, amr); Associated with Inborn genetic diseases.

What condition is associated with SECISBP2 p.Ser46Phe (c.137C>T)?

SECISBP2 p.Ser46Phe (c.137C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SECISBP2 p.Ser46Phe (c.137C>T) in the general population?

SECISBP2 p.Ser46Phe (c.137C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about SECISBP2 p.Ser46Phe (c.137C>T)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

SECISBP2 p.Ser46Phe

c.137C>T · rs1027713548 · VCV3159405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.57, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	19.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,012 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00112% 18/1,614,092 alleles · ultra-rare exomes 8/1,461,862 · genomes 10/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,456
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.004%	24,977
European (non-Finnish)	8.47e-05%	1,180,026

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: SECISBP2
Protein: p.Ser46Phe
Coding: c.137C>T
MANE Select: NM_024077
dbSNP: rs1027713548
Type: single nucleotide variant
Location: chr9:89319752 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.54 · 2 PDB

Full SECISBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SECISBP2 p.Ser46Cys Uncertain significance ★ ⚠ same residue
SECISBP2 p.Gln799Lys Uncertain significance ★★ ⚠ same condition
SECISBP2 p.Ser346Phe Uncertain significance ★★ ⚠ same condition
SECISBP2 p.Ala18Val Uncertain significance ★ ⚠ same condition
SECISBP2 p.Ala262Thr Uncertain significance ★ ⚠ same condition
SECISBP2 p.Ala366Thr Uncertain significance ★ ⚠ same condition
SECISBP2 p.Ala40Glu Uncertain significance ★ ⚠ same condition
SECISBP2 p.Ala458Thr 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/secisbp2-p-ser46phe (accessed [today's date]).

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