Is SLX4 p.Pro600= (c.1800G>A) pathogenic?

SLX4 p.Pro600= (c.1800G>A) is classified Likely benign in SLX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-02). Very rare (popmax 0.00472%, eas); Associated with Fanconi anemia.

What condition is associated with SLX4 p.Pro600= (c.1800G>A)?

SLX4 p.Pro600= (c.1800G>A) is associated with Fanconi anemia (ClinVar).

How common is SLX4 p.Pro600= (c.1800G>A) in the general population?

SLX4 p.Pro600= (c.1800G>A) is very rare (popmax 0.00472%, eas) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

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

SLX4 p.Pro600=

c.1800G>A · rs777829533 · VCV241667

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00472%, eas)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -3.6
Overall
CADD	0.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00472% East Asian · 2/42,348 alleles

Filtering AF 0.00168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.00233% 33/1,413,986 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00472%	21,174
African / African-American	0.0027%	37,027
European (non-Finnish)	0.00242%	41,311
South Asian	0.00117%	85,668

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: SLX4
Protein: p.Pro600=
Coding: c.1800G>A
MANE Select: NM_032444
dbSNP: rs777829533
Type: single nucleotide variant
Location: chr16:3596277 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.20 · 7 PDB
Residue 600: the 'interaction with slx4ip, ercc4/xpf and msh2' 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

SLX4 p.Pro600Gln Uncertain significance ★★ ⚠ same residue
SLX4 p.Pro600Leu Uncertain significance ★★ ⚠ same residue
SLX4 p.Pro600Ser Uncertain significance ★ ⚠ same residue
SLX4 c.1684-1G>A Likely pathogenic ★★ same condition
SLX4 p.Arg1666Ter Pathogenic/Likely pathogenic ★★ same condition
SLX4 p.Arg481Ter Pathogenic/Likely pathogenic ★★ same condition
SLX4 p.Arg713Ter Pathogenic/Likely pathogenic ★★ same condition
SLX4 p.Gln1201Ter 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-pro600 (accessed [today's date]).

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