Is SLMAP p.Leu747= (c.2241T>C) pathogenic?

SLMAP p.Leu747= (c.2241T>C) is classified Likely benign in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-24). Very rare (popmax 0.00769%, sas).

How common is SLMAP p.Leu747= (c.2241T>C) in the general population?

SLMAP p.Leu747= (c.2241T>C) is very rare (popmax 0.00769%, sas) (gnomAD).

SLMAP p.Leu747=

c.2241T>C · rs764765206 · VCV1786526

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.163	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.3, phastCons 1
Overall
CADD	8.168	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,076 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000434% 7/1,613,924 alleles · very rare exomes 7/1,461,704 · genomes 0/152,220 · 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.Leu747=
Coding: c.2241T>C
MANE Select: NM_001377540
dbSNP: rs764765206
Type: single nucleotide variant
Location: chr3:57917008 (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-leu747 (accessed [today's date]).

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