Is SLMAP p.Glu486Val (c.1457A>T) pathogenic?

SLMAP p.Glu486Val (c.1457A>T) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). AlphaMissense: likely benign (0.2631); Ultra-rare (popmax 0.0118%, amr).

How common is SLMAP p.Glu486Val (c.1457A>T) in the general population?

SLMAP p.Glu486Val (c.1457A>T) is ultra-rare (popmax 0.0118%, amr) (gnomAD).

What do computational predictors say about SLMAP p.Glu486Val (c.1457A>T)?

AlphaMissense predicts likely benign (score 0.2631) — an in-silico prediction, not a clinical call.

SLMAP p.Glu486Val

c.1457A>T · rs764183885 · VCV3225998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2631 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2631	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E469V vs ClinVar E486V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% Admixed American · 7/59,122 alleles

Filtering AF 0.00551% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00385%

Overall 0.000435% 7/1,610,210 alleles · ultra-rare exomes 7/1,457,892 · genomes 0/152,318 · 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.Glu486Val
Coding: c.1457A>T
MANE Select: NM_001377540
dbSNP: rs764183885
Type: single nucleotide variant
Location: chr3:57896888 (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-glu486val (accessed [today's date]).

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