Is SERPINE3 p.Val246Met (c.736G>A) pathogenic?

SERPINE3 p.Val246Met (c.736G>A) is classified Uncertain significance in SERPINE3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.3154); Absent from gnomAD v4.1.

How common is SERPINE3 p.Val246Met (c.736G>A) in the general population?

SERPINE3 p.Val246Met (c.736G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SERPINE3 p.Val246Met (c.736G>A)?

AlphaMissense predicts likely benign (score 0.3154) — an in-silico prediction, not a clinical call.

SERPINE3 p.Val246Met

c.736G>A · rs559197473 · VCV2607394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3154 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3154	likely benign
REVEL	0.605	indeterminate
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -2.1, phastCons 0.001
Regional constraint	o/e 0.89	unconstrained · MANE · 23 kb · p 0.02 · regional, not allelic
Overall
CADD	18.98	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

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: SERPINE3
Protein: p.Val246Met
Coding: c.736G>A
MANE Select: NM_001386375
dbSNP: rs559197473
Type: single nucleotide variant
Location: chr13:51348248 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.41

Full SERPINE3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SERPINE3 p.Ala255Ser Uncertain significance ★ ⚠ same type
SERPINE3 p.Ala34Ser Uncertain significance ★ ⚠ same type
SERPINE3 p.Ala377Val Uncertain significance ★ ⚠ same type
SERPINE3 p.Ala43Thr Uncertain significance ★ ⚠ same type
SERPINE3 p.Ala68Thr Uncertain significance ★ ⚠ same type
SERPINE3 p.Arg23Cys Uncertain significance ★ ⚠ same type
SERPINE3 p.Arg369Thr Uncertain significance ★ same type
SERPINE3 p.Arg371Gln Uncertain significance ★ ⚠ 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/serpine3-p-val246met (accessed [today's date]).

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