Is SLX4 p.Pro647= (c.1941C>T) pathogenic?

SLX4 p.Pro647= (c.1941C>T) is classified Conflicting classifications of pathogenicity in SLX4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-28). Ultra-rare (popmax 0.0846%, sas); Associated with Fanconi anemia complementation group P.

What condition is associated with SLX4 p.Pro647= (c.1941C>T)?

SLX4 p.Pro647= (c.1941C>T) is associated with Fanconi anemia complementation group P, Fanconi anemia (ClinVar).

How common is SLX4 p.Pro647= (c.1941C>T) in the general population?

SLX4 p.Pro647= (c.1941C>T) is ultra-rare (popmax 0.0846%, sas) (gnomAD).

SLX4 p.Pro647=

c.1941C>T · rs540288743 · VCV319171

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0846%, sas)

Conditions

Fanconi anemia complementation group P

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 -0.48	GERP -3.6
Overall
CADD	3.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0846% South Asian · 77/91,066 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00651% 105/1,614,022 alleles · ultra-rare exomes 92/1,461,762 · genomes 13/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0846%	1,183
Admixed American	0.02%	5,002
African / African-American	0.0107%	9,380
Remaining individualsnot grpmax-eligible	0.0096%	10,417
East Asian	0.00223%	44,858
European (non-Finnish)	8.47e-05%	1,180,030

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.Pro647=
Coding: c.1941C>T
MANE Select: NM_032444
dbSNP: rs540288743
Type: single nucleotide variant
Location: chr16:3595677 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.20 · 7 PDB
Residue 647: 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 complementation group P — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia

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

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-pro647 (accessed [today's date]).

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