Is SECISBP2 p.Pro44Leu (c.131C>T) pathogenic?

SECISBP2 p.Pro44Leu (c.131C>T) is classified Uncertain significance in SECISBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.1626); No allele count reported in gnomAD v4.1 (AN 1,614,060); Associated with Inborn genetic diseases.

What condition is associated with SECISBP2 p.Pro44Leu (c.131C>T)?

SECISBP2 p.Pro44Leu (c.131C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SECISBP2 p.Pro44Leu (c.131C>T) in the general population?

SECISBP2 p.Pro44Leu (c.131C>T) is no allele count reported in gnomAD v4.1 (AN 1,614,060) (gnomAD).

What do computational predictors say about SECISBP2 p.Pro44Leu (c.131C>T)?

AlphaMissense predicts likely benign (score 0.1626) — an in-silico prediction, not a clinical call.

SECISBP2 p.Pro44Leu

c.131C>T · VCV3951890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1626 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,060)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1626	likely benign
REVEL	0.608	indeterminate
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.73, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,614,060). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SECISBP2
Protein: p.Pro44Leu
Coding: c.131C>T
MANE Select: NM_024077
Type: single nucleotide variant
Location: chr9:89319746 (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.Pro44Ser 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-pro44leu (accessed [today's date]).

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