Is F13A1 p.Leu599Pro (c.1796T>C) pathogenic?

F13A1 p.Leu599Pro (c.1796T>C) is classified Uncertain significance in F13A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-05). AlphaMissense: likely pathogenic (0.6841); Absent from gnomAD v4.1.

How common is F13A1 p.Leu599Pro (c.1796T>C) in the general population?

F13A1 p.Leu599Pro (c.1796T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F13A1 p.Leu599Pro (c.1796T>C)?

AlphaMissense predicts likely pathogenic (score 0.6841) — an in-silico prediction, not a clinical call.

F13A1 p.Leu599Pro

c.1796T>C · rs2480517632 · VCV3063775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6841	likely pathogenic
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 173 kb · p 0.0002 · regional, not allelic
Overall
CADD	26.0	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: F13A1
Protein: p.Leu599Pro
Coding: c.1796T>C
MANE Select: NM_000129
dbSNP: rs2480517632
Type: single nucleotide variant
Location: chr6:6167570 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.15 · 15 PDB

Full F13A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F13A1 c.691-1G>A Pathogenic/Likely pathogenic ★★ same type
F13A1 p.Arg327Gln Pathogenic/Likely pathogenic ★★ same type
F13A1 p.Arg409Gln Likely pathogenic ★★ ⚠ same type
F13A1 p.Arg662Ter Pathogenic ★★ same type
F13A1 p.Arg682His Pathogenic ★★ ⚠ same type
F13A1 p.Arg78Cys Pathogenic/Likely pathogenic ★★ same type
F13A1 p.Gly274Arg Likely pathogenic ★★ same type
F13A1 c.*1045C>G 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/f13a1-p-leu599pro (accessed [today's date]).

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