Is SLX4 p.Pro385= (c.1155C>T) pathogenic?

SLX4 p.Pro385= (c.1155C>T) is classified Likely benign in SLX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-02). Ultra-rare (popmax 0.0169%, mid); Associated with Fanconi anemia.

What condition is associated with SLX4 p.Pro385= (c.1155C>T)?

SLX4 p.Pro385= (c.1155C>T) is associated with Fanconi anemia (ClinVar).

How common is SLX4 p.Pro385= (c.1155C>T) in the general population?

SLX4 p.Pro385= (c.1155C>T) is ultra-rare (popmax 0.0169%, mid) (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.Pro385=

c.1155C>T · rs763763182 · VCV1594171

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -3.9
Overall
CADD	0.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% Middle Eastern · 1/5,928 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,476 alleles · ultra-rare exomes 9/1,461,366 · genomes 1/152,110 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,928
South Asian	0.0011%	91,028
European (non-Finnish)	0.000678%	147,497

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.Pro385=
Coding: c.1155C>T
MANE Select: NM_032444
dbSNP: rs763763182
Type: single nucleotide variant
Location: chr16:3600987 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.20 · 7 PDB
Residue 385: the 'interaction with slx4ip, ercc4/xpf and msh2' region; the 'disordered' region; a UniProt-annotated variant site (in)

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.Pro385Thr Benign/Likely benign ★★ 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
SLX4 p.Gln1306Ter Pathogenic ★★ same condition
SLX4 p.Gln1386Ter 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-pro385 (accessed [today's date]).

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