Is SLX4 p.Pro602= (c.1806T>C) pathogenic?

SLX4 p.Pro602= (c.1806T>C) is classified Likely benign in SLX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). Very rare (popmax 0.00311%, nfe); Associated with Fanconi anemia.

What condition is associated with SLX4 p.Pro602= (c.1806T>C)?

SLX4 p.Pro602= (c.1806T>C) is associated with Fanconi anemia (ClinVar).

How common is SLX4 p.Pro602= (c.1806T>C) in the general population?

SLX4 p.Pro602= (c.1806T>C) is very rare (popmax 0.00311%, nfe) (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.Pro602=

c.1806T>C · rs925073189 · VCV1561913

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00311%, nfe)

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 -1.4	GERP -3.6
Overall
CADD	0.695	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00311% European (non-Finnish) · 36/1,155,982 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00243% 38/1,564,612 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00311%	32,111
Remaining individualsnot grpmax-eligible	0.00165%	60,640
African / African-American	0.00135%	73,854

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: SLX4
Protein: p.Pro602=
Coding: c.1806T>C
MANE Select: NM_032444
dbSNP: rs925073189
Type: single nucleotide variant
Location: chr16:3596271 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.20 · 7 PDB
Residue 602: 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.Pro602Arg Uncertain significance ★★ ⚠ same residue
SLX4 p.Pro602Ala Uncertain significance ★ ⚠ same residue
SLX4 p.Pro602Leu 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-pro602 (accessed [today's date]).

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