Is SLMAP p.Leu809Pro (c.2426T>C) pathogenic?

SLMAP p.Leu809Pro (c.2426T>C) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely pathogenic (0.9155); Absent from gnomAD v4.1.

How common is SLMAP p.Leu809Pro (c.2426T>C) in the general population?

SLMAP p.Leu809Pro (c.2426T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLMAP p.Leu809Pro (c.2426T>C)?

AlphaMissense predicts likely pathogenic (score 0.9155) — an in-silico prediction, not a clinical call.

SLMAP p.Leu809Pro

c.2426T>C · rs2476550403 · VCV3226005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9155 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9155	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -10.35	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L792P vs ClinVar L809P) — verify the residue.

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: SLMAP
Protein: p.Leu809Pro
Coding: c.2426T>C
MANE Select: NM_001377540
dbSNP: rs2476550403
Type: single nucleotide variant
Location: chr3:57923004 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.74 · 3 PDB

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

Similar variants

SLMAP p.Leu809= Likely benign ★ same residue
SLMAP c.*38C>T Uncertain significance ★★ ⚠ same type
SLMAP c.*55G>A Uncertain significance ★★ ⚠ same type
SLMAP c.*70G>A Uncertain significance ★★ ⚠ same type
SLMAP p.Ala365Asp Uncertain significance ★★ ⚠ same type
SLMAP p.Ala506Ser Uncertain significance ★★ ⚠ same type
SLMAP p.Ala597Val Uncertain significance ★★ ⚠ same type
SLMAP p.Arg136Gln 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/slmap-p-leu809pro (accessed [today's date]).

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