Is SLX4 p.Pro342= (c.1026G>A) pathogenic?

SLX4 p.Pro342= (c.1026G>A) is classified Likely benign in SLX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-30). Ultra-rare (popmax 0.0164%, mid); Associated with Fanconi anemia.

What condition is associated with SLX4 p.Pro342= (c.1026G>A)?

SLX4 p.Pro342= (c.1026G>A) is associated with Fanconi anemia (ClinVar).

How common is SLX4 p.Pro342= (c.1026G>A) in the general population?

SLX4 p.Pro342= (c.1026G>A) is ultra-rare (popmax 0.0164%, 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.Pro342=

c.1026G>A · rs755211335 · VCV701804

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -11	GERP -3.9
Overall
CADD	0.586	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00161% 26/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00667%	14,997
South Asian	0.00659%	15,181
African / African-American	0.00267%	37,454
Remaining individualsnot grpmax-eligible	0.0016%	62,490
Finnishnot grpmax-eligible	0.00156%	64,006
European (non-Finnish)	0.000932%	107,277

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.Pro342=
Coding: c.1026G>A
MANE Select: NM_032444
dbSNP: rs755211335
Type: single nucleotide variant
Location: chr16:3601116 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.20 · 7 PDB
Residue 342: the 'interaction with slx4ip, ercc4/xpf and msh2' 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.Pro342Leu 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
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-pro342 (accessed [today's date]).

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