FAP p.Pro216Leu
c.647C>T · VCV3513024
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4143 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4143 | ambiguous |
|---|---|---|
| REVEL | 0.9 | moderately pathogenic-leaning |
| SaProt | LLR -11.52 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.9, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 72 kb · p 0.75 · regional, not allelic |
| Overall | ||
| CADD | 27.9 | 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
- FAP
- Protein
- p.Pro216Leu
- Coding
- c.647C>T
- MANE Select
- NM_004460
- Type
- single nucleotide variant
- Location
- chr2:162218101 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.72 · 4 PDB
Similar variants
- FAP c.1870-8C>A Benign ★★ same type
- FAP p.Ala100= Benign ★★ same type
- FAP p.Gln708= Benign ★★ same type
- FAP p.Gly195= Benign ★★ same type
- FAP p.Leu212Phe Benign ★★ ⚠ same type
- FAP p.Phe185Leu Likely benign ★★ ⚠ same type
- FAP p.Ser737= Likely benign ★★ same type
- FAP p.Thr229Met Benign ★★ ⚠ 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/fap-p-pro216leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown