Is SLX4 p.Ala1726Val (c.5177C>T) pathogenic?

SLX4 p.Ala1726Val (c.5177C>T) is classified Conflicting classifications of pathogenicity in SLX4 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-01-25). AlphaMissense: likely benign (0.119); Rare (popmax 0.107%, eas); Associated with Fanconi anemia.

What condition is associated with SLX4 p.Ala1726Val (c.5177C>T)?

SLX4 p.Ala1726Val (c.5177C>T) is associated with Fanconi anemia, Fanconi anemia complementation group P (ClinVar).

How common is SLX4 p.Ala1726Val (c.5177C>T) in the general population?

SLX4 p.Ala1726Val (c.5177C>T) is rare (popmax 0.107%, 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.

What do computational predictors say about SLX4 p.Ala1726Val (c.5177C>T)?

AlphaMissense predicts likely benign (score 0.119) — an in-silico prediction, not a clinical call.

SLX4 p.Ala1726Val

c.5177C>T · rs752633436 · VCV843315

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.119 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.119	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.43	GERP -2.7
Regional constraint	o/e 1.07	unconstrained · MANE · 27 kb · p 0.0005 · regional, not allelic
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% East Asian · 48/44,884 alleles

Filtering AF 0.0829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0743%

Overall 0.00384% 62/1,612,682 alleles · rare exomes 56/1,460,356 · genomes 6/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.107%	935
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,832
Admixed American	0.00333%	30,005
South Asian	0.0022%	45,540
European (non-Finnish)	0.000508%	196,664

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.Ala1726Val
Coding: c.5177C>T
MANE Select: NM_032444
dbSNP: rs752633436
Type: single nucleotide variant
Location: chr16:3582670 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.20 · 7 PDB
Residue 1726: the 'interaction with plk1 and terf2-terf2ip' region; the 'disordered' region; the 'interaction with slx1' 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

Also linked: Fanconi anemia complementation group P

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

SLX4 p.Ala1726= Likely benign ★★ same residue
SLX4 c.1684-1G>A Likely pathogenic ★★ same condition
SLX4 c.951-1G>T 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

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-ala1726val (accessed [today's date]).

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