Is SERPING1 p.Leu151= (c.451C>T) pathogenic?

SERPING1 p.Leu151= (c.451C>T) is classified Benign/Likely benign in SERPING1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-17). Rare (popmax 0.123%, amr); Associated with Inborn genetic diseases.

What condition is associated with SERPING1 p.Leu151= (c.451C>T)?

SERPING1 p.Leu151= (c.451C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SERPING1 p.Leu151= (c.451C>T) in the general population?

SERPING1 p.Leu151= (c.451C>T) is rare (popmax 0.123%, amr) (gnomAD).

SERPING1 p.Leu151=

c.451C>T · rs747802289 · VCV699572

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, amr)

Conditions

Inborn genetic diseases

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 -0.11	GERP -3.1
Overall
CADD	5.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% Admixed American · 74/60,000 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0924%

Overall 0.00502% 81/1,613,990 alleles · rare exomes 74/1,461,810 · genomes 7/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.123%	811
Remaining individualsnot grpmax-eligible	0.0112%	8,926

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: SERPING1
Protein: p.Leu151=
Coding: c.451C>T
MANE Select: NM_000062
dbSNP: rs747802289
Type: single nucleotide variant
Location: chr11:57600278 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 151: an α-helix

Full SERPING1 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

SERPING1 p.Leu151Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
SERPING1 c.51+3A>G Pathogenic ★★ same condition
SERPING1 p.Asp408Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
SERPING1 p.Pro498Leu Likely pathogenic ★★ ⚠ same condition
SERPING1 p.Asp144Gly Uncertain significance ★★ ⚠ same condition
SERPING1 p.Asp424Glu Uncertain significance ★★ ⚠ same condition
SERPING1 p.Gln180His Uncertain significance ★★ ⚠ same condition
SERPING1 p.His334Tyr 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/serping1-p-leu151 (accessed [today's date]).

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