Is SLMAP p.Leu356Phe (c.1066C>T) pathogenic?

SLMAP p.Leu356Phe (c.1066C>T) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-31). AlphaMissense: likely pathogenic (0.6376); Very rare (popmax 0.00407%, afr).

How common is SLMAP p.Leu356Phe (c.1066C>T) in the general population?

SLMAP p.Leu356Phe (c.1066C>T) is very rare (popmax 0.00407%, afr) (gnomAD).

What do computational predictors say about SLMAP p.Leu356Phe (c.1066C>T)?

AlphaMissense predicts likely pathogenic (score 0.6376) — an in-silico prediction, not a clinical call.

SLMAP p.Leu356Phe

c.1066C>T · rs1470689481 · VCV2448005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6376 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6376	likely pathogenic
REVEL	0.284	benign-leaning
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 94 kb · p 9.6e-06 · 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

Grpmax group 0.00407% African / African-American · 3/73,658 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0005%

Overall 0.00025% 4/1,598,804 alleles · very rare exomes 3/1,446,748 · genomes 1/152,056 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00407%	24,553
Remaining individualsnot grpmax-eligible	0.00162%	61,854

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.Leu356Phe
Coding: c.1066C>T
MANE Select: NM_001377540
dbSNP: rs1470689481
Type: single nucleotide variant
Location: chr3:57864647 (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-leu356phe (accessed [today's date]).

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