Is SLX4 p.Pro930Arg (c.2789C>G) pathogenic?

SLX4 p.Pro930Arg (c.2789C>G) is classified Uncertain significance in SLX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.0799); Absent from gnomAD v4.1; Associated with Fanconi anemia.

What condition is associated with SLX4 p.Pro930Arg (c.2789C>G)?

SLX4 p.Pro930Arg (c.2789C>G) is associated with Fanconi anemia (ClinVar).

How common is SLX4 p.Pro930Arg (c.2789C>G) in the general population?

SLX4 p.Pro930Arg (c.2789C>G) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SLX4 p.Pro930Arg (c.2789C>G)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

SLX4 p.Pro930Arg

c.2789C>G · rs2548213890 · VCV1930627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.63	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 0.32	GERP -3.9
Regional constraint	o/e 1.07	unconstrained · MANE · 27 kb · p 0.0005 · regional, not allelic
Overall
CADD	3.597	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLX4
Protein: p.Pro930Arg
Coding: c.2789C>G
MANE Select: NM_032444
dbSNP: rs2548213890
Type: single nucleotide variant
Location: chr16:3590849 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.20 · 7 PDB
Residue 930: the 'interaction with plk1 and terf2-terf2ip' region; the 'disordered' region

Full SLX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fanconi anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

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SLX4 p.Arg481Ter Pathogenic/Likely pathogenic ★★ same condition
SLX4 p.Arg713Ter Pathogenic/Likely pathogenic ★★ same condition
SLX4 p.Gln1201Ter Pathogenic/Likely pathogenic ★★ same condition
SLX4 p.Gln1306Ter Pathogenic ★★ same condition
SLX4 p.Gln1386Ter Pathogenic/Likely pathogenic ★★ same condition
SLX4 p.Gln187Ter Pathogenic/Likely pathogenic ★★ 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/slx4-p-pro930arg (accessed [today's date]).

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