Is SECISBP2 p.Ser472Pro (c.1414T>C) pathogenic?

SECISBP2 p.Ser472Pro (c.1414T>C) is classified Uncertain significance in SECISBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.1207); Ultra-rare (popmax 0.022%, sas); Associated with Inborn genetic diseases.

What condition is associated with SECISBP2 p.Ser472Pro (c.1414T>C)?

SECISBP2 p.Ser472Pro (c.1414T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SECISBP2 p.Ser472Pro (c.1414T>C) in the general population?

SECISBP2 p.Ser472Pro (c.1414T>C) is ultra-rare (popmax 0.022%, sas) (gnomAD).

What do computational predictors say about SECISBP2 p.Ser472Pro (c.1414T>C)?

AlphaMissense predicts likely benign (score 0.1207) — an in-silico prediction, not a clinical call.

SECISBP2 p.Ser472Pro

c.1414T>C · rs763829903 · VCV2265457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1207 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1207	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -6.69	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 1.8	GERP 0.87, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	21.9	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 0.022% South Asian · 20/91,094 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00124% 20/1,614,040 alleles · ultra-rare exomes 19/1,461,828 · genomes 1/152,212 · joint denominator

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.Ser472Pro
Coding: c.1414T>C
MANE Select: NM_024077
dbSNP: rs763829903
Type: single nucleotide variant
Location: chr9:89341458 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.54 · 2 PDB
Residue 472: a turn

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.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
SECISBP2 p.Ala512Thr 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-ser472pro (accessed [today's date]).

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