Is LRP12 p.Pro676Ser (c.2026C>T) pathogenic?

LRP12 p.Pro676Ser (c.2026C>T) is classified Uncertain significance in LRP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.2556); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LRP12 p.Pro676Ser (c.2026C>T)?

LRP12 p.Pro676Ser (c.2026C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRP12 p.Pro676Ser (c.2026C>T) in the general population?

LRP12 p.Pro676Ser (c.2026C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRP12 p.Pro676Ser (c.2026C>T)?

AlphaMissense predicts likely benign (score 0.2556) — an in-silico prediction, not a clinical call.

LRP12 p.Pro676Ser

c.2026C>T · VCV4048623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2556 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2556	likely benign
REVEL	0.512	indeterminate
SaProt	LLR -6.07	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 18 kb · p 1.2e-07 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRP12
Protein: p.Pro676Ser
Coding: c.2026C>T
MANE Select: NM_013437
Type: single nucleotide variant
Location: chr8:104491227 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.10
Residue 676: the 'disordered' region

Full LRP12 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

LRP12 p.Arg732Cys Uncertain significance ★★ ⚠ same condition
LRP12 p.Ala204Gly Uncertain significance ★ ⚠ same condition
LRP12 p.Ala2Val Uncertain significance ★ ⚠ same condition
LRP12 p.Ala554Ser Uncertain significance ★ ⚠ same condition
LRP12 p.Ala684Val Uncertain significance ★ ⚠ same condition
LRP12 p.Ala82Thr Uncertain significance ★ ⚠ same condition
LRP12 p.Arg102Ser Uncertain significance ★ ⚠ same condition
LRP12 p.Arg172Cys 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/lrp12-p-pro676ser (accessed [today's date]).

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