Is SERPING1 p.Pro94fs (c.279dup) pathogenic?

SERPING1 p.Pro94fs (c.279dup) is classified Benign/Likely benign in SERPING1 (ClinVar, No assertion criteria, 2 submitters). Ultra-rare (popmax 0.0325%, nfe).

How common is SERPING1 p.Pro94fs (c.279dup) in the general population?

SERPING1 p.Pro94fs (c.279dup) is ultra-rare (popmax 0.0325%, nfe) (gnomAD).

SERPING1 p.Pro94fs

c.279dup · rs1945330983 · VCV1206404

Benign/Likely benign No assertion criteria

Classification

Benign/Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0325%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.48	GERP 0.28
Overall
CADD	15.58	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	AACCCACCACAC simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0325% European (non-Finnish) · 370/1,139,226 alleles

Filtering AF 0.0297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.0268% 421/1,569,056 alleles · ultra-rare exomes 407/1,417,208 · genomes 14/151,848 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0325%	3,079
Remaining individualsnot grpmax-eligible	0.018%	5,547
African / African-American	0.0176%	5,693
Middle Eastern	0.0167%	5,994
South Asian	0.0144%	6,931
East Asian	0.00896%	11,158
Ashkenazi Jewishnot grpmax-eligible	0.00681%	14,678
Finnishnot grpmax-eligible	0.00626%	15,984
Admixed American	0.00501%	19,957

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.Pro94fs
Coding: c.279dup
MANE Select: NM_000062
dbSNP: rs1945330983
Type: Duplication
Location: chr11:57600105 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 94: the 'disordered' region; the '7 x 4 aa tandem repeats of [qe]-p-t-[tq]' region; a UniProt-annotated variant site (in hae1; phenotype consistent with hereditary angioedema type 2)

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

Similar variants

SERPING1 p.Pro94Thr Uncertain significance ★ ⚠ same residue
SERPING1 p.Glu451fs Pathogenic ★★ same type
SERPING1 p.Lys201fs Pathogenic ★★ same type
SERPING1 p.Thr128fs Pathogenic ★★ same type
SERPING1 c.685+4dup Likely pathogenic ★ same type
SERPING1 p.Ala209fs Pathogenic ★ same type
SERPING1 p.Arg249fs Pathogenic ★ same type
SERPING1 p.Asn271fs 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-pro94fs (accessed [today's date]).

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