Is SERPING1 p.Val45Phe (c.133G>T) pathogenic?

SERPING1 p.Val45Phe (c.133G>T) is classified Likely benign in SERPING1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0745); Ultra-rare (popmax 0.044%, afr).

How common is SERPING1 p.Val45Phe (c.133G>T) in the general population?

SERPING1 p.Val45Phe (c.133G>T) is ultra-rare (popmax 0.044%, afr) (gnomAD).

What do computational predictors say about SERPING1 p.Val45Phe (c.133G>T)?

AlphaMissense predicts likely benign (score 0.0745) — an in-silico prediction, not a clinical call.

SERPING1 p.Val45Phe

c.133G>T · rs143231506 · VCV1096580

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0745 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0745	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.6	GERP -4.5
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.044% African / African-American · 33/74,916 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.00527% 85/1,614,074 alleles · ultra-rare exomes 55/1,461,892 · genomes 30/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.044%	2,270
Middle Eastern	0.0329%	3,042
Admixed American	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0096%	10,415
European (non-Finnish)	0.00237%	42,145

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.Val45Phe
Coding: c.133G>T
MANE Select: NM_000062
dbSNP: rs143231506
Type: single nucleotide variant
Location: chr11:57599960 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB

Full SERPING1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SERPING1 p.Val45= Uncertain significance ★ same residue
SERPING1 p.Val45Ala Uncertain significance ★ ⚠ same residue
SERPING1 c.1030-1G>T Pathogenic ★★ same type
SERPING1 c.51+1G>T Pathogenic ★★ same type
SERPING1 c.51+3A>C Pathogenic/Likely pathogenic ★★ same type
SERPING1 c.51+3A>G Pathogenic ★★ same type
SERPING1 c.52-1G>A Pathogenic ★★ same type
SERPING1 c.550+1G>A Pathogenic ★★ same type

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-val45phe (accessed [today's date]).

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