Is SERPING1 p.Ser350Phe (c.1049C>T) pathogenic?

SERPING1 p.Ser350Phe (c.1049C>T) is classified Uncertain significance in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: ambiguous (0.3687); Very rare (popmax 0.00119%, nfe).

How common is SERPING1 p.Ser350Phe (c.1049C>T) in the general population?

SERPING1 p.Ser350Phe (c.1049C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about SERPING1 p.Ser350Phe (c.1049C>T)?

AlphaMissense predicts ambiguous (score 0.3687) — an in-silico prediction, not a clinical call.

SERPING1 p.Ser350Phe

c.1049C>T · rs369960628 · VCV1473863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3687	ambiguous
REVEL	0.625	indeterminate
SaProt	LLR -11.09	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	24.7	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 0.00119% European (non-Finnish) · 14/1,179,996 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,614,140 alleles · very rare exomes 14/1,461,846 · genomes 0/152,294 · joint denominator

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.Ser350Phe
Coding: c.1049C>T
MANE Select: NM_000062
dbSNP: rs369960628
Type: single nucleotide variant
Location: chr11:57611736 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 350: a β-strand

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

Similar variants

SERPING1 p.Ser350Pro Likely 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-ser350phe (accessed [today's date]).

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