Is SLMAP p.Glu545Lys (c.1633G>A) pathogenic?

SLMAP p.Glu545Lys (c.1633G>A) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely benign (0.28); Very rare (popmax 0.00383%, nfe).

How common is SLMAP p.Glu545Lys (c.1633G>A) in the general population?

SLMAP p.Glu545Lys (c.1633G>A) is very rare (popmax 0.00383%, nfe) (gnomAD).

What do computational predictors say about SLMAP p.Glu545Lys (c.1633G>A)?

AlphaMissense predicts likely benign (score 0.28) — an in-silico prediction, not a clinical call.

SLMAP p.Glu545Lys

c.1633G>A · rs1409531494 · VCV1774639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.28 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00383%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.28	likely benign
REVEL	0.284	benign-leaning
SaProt	LLR -10.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	32.0	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 E528K vs ClinVar E545K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00383% European (non-Finnish) · 45/1,175,812 alleles

Filtering AF 0.00292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.0028% 45/1,607,688 alleles · very rare exomes 43/1,455,614 · genomes 2/152,074 · 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: SLMAP
Protein: p.Glu545Lys
Coding: c.1633G>A
MANE Select: NM_001377540
dbSNP: rs1409531494
Type: single nucleotide variant
Location: chr3:57909084 (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 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
SLMAP p.Arg138Cys 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-glu545lys (accessed [today's date]).

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