Is SERPING1 p.His136Arg (c.407A>G) pathogenic?

SERPING1 p.His136Arg (c.407A>G) is classified Uncertain significance in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-06). AlphaMissense: likely benign (0.0519); Absent from gnomAD v4.1.

How common is SERPING1 p.His136Arg (c.407A>G) in the general population?

SERPING1 p.His136Arg (c.407A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SERPING1 p.His136Arg (c.407A>G)?

AlphaMissense predicts likely benign (score 0.0519) — an in-silico prediction, not a clinical call.

SERPING1 p.His136Arg

c.407A>G · VCV4767046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0519 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0519	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -4.45	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 -1.5	GERP -4.5
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	0.083	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: SERPING1
Protein: p.His136Arg
Coding: c.407A>G
MANE Select: NM_000062
Type: single nucleotide variant
Location: chr11:57600234 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 136: a UniProt-annotated variant site (in hae1; phenotype consistent with hereditary angioedema type 2); an α-helix

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

Similar variants

SERPING1 p.His136fs Pathogenic ★ 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
SERPING1 c.551-1G>C Pathogenic/Likely 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-his136arg (accessed [today's date]).

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