Is SLF2 p.Ile703Val (c.2107A>G) pathogenic?

SLF2 p.Ile703Val (c.2107A>G) is classified Uncertain significance in SLF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-17). AlphaMissense: likely benign (0.0687); Ultra-rare (popmax 0.0112%, eas); Associated with Inborn genetic diseases.

What condition is associated with SLF2 p.Ile703Val (c.2107A>G)?

SLF2 p.Ile703Val (c.2107A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SLF2 p.Ile703Val (c.2107A>G) in the general population?

SLF2 p.Ile703Val (c.2107A>G) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about SLF2 p.Ile703Val (c.2107A>G)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

SLF2 p.Ile703Val

c.2107A>G · rs746661266 · VCV2475943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -5.6, phastCons 0.001
Regional constraint	o/e 0.85	unconstrained · MANE · 37 kb · p 0.0001 · regional, not allelic
Overall
CADD	4.289	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,818 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00089% 13/1,460,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,964
South Asian	0.0022%	45,508
Admixed American	0.00167%	60,006
European (non-Finnish)	0.000424%	235,884

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: SLF2
Protein: p.Ile703Val
Coding: c.2107A>G
MANE Select: NM_018121
dbSNP: rs746661266
Type: single nucleotide variant
Location: chr10:100929381 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.80 · 1 PDB
Residue 703: a UniProt-annotated variant site (in atels1); the 'interaction with simc1' region; the 'nse6-like domain' region; the 'required for interaction with slf1 and rad18' region

Full SLF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLF2 p.Gln756Arg Uncertain significance ★★ ⚠ same condition
SLF2 p.Leu441Ile Uncertain significance ★★ ⚠ same condition
SLF2 c.3486+22T>G Uncertain significance ★ same condition
SLF2 p.Ala1145Thr Uncertain significance ★ ⚠ same condition
SLF2 p.Ala139Val Uncertain significance ★ ⚠ same condition
SLF2 p.Ala526Thr Uncertain significance ★ ⚠ same condition
SLF2 p.Ala644Val Uncertain significance ★ ⚠ same condition
SLF2 p.Arg1046Cys Uncertain significance ★ ⚠ same condition

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/slf2-p-ile703val (accessed [today's date]).

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