Is ASPN p.Leu243= (c.727T>C) pathogenic?

ASPN p.Leu243= (c.727T>C) is classified Likely benign in ASPN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-20). Very rare (popmax 0.00894%, eas); Associated with ASPN-related disorder.

What condition is associated with ASPN p.Leu243= (c.727T>C)?

ASPN p.Leu243= (c.727T>C) is associated with ASPN-related disorder (ClinVar).

How common is ASPN p.Leu243= (c.727T>C) in the general population?

ASPN p.Leu243= (c.727T>C) is very rare (popmax 0.00894%, eas) (gnomAD).

ASPN p.Leu243=

c.727T>C · rs539600204 · VCV3052688

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00894%, eas)

Conditions

ASPN-related disorder

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 -1.1
Overall
CADD	1.463	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00894% East Asian · 4/44,746 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000943% 15/1,590,402 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00894%	11,186
Remaining individualsnot grpmax-eligible	0.00486%	20,568
African / African-American	0.00134%	74,550
South Asian	0.00111%	90,422
European (non-Finnish)	0.000518%	193,103

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: ASPN
Protein: p.Leu243=
Coding: c.727T>C
MANE Select: NM_017680
dbSNP: rs539600204
Type: single nucleotide variant
Location: chr9:92460550 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.71

Full ASPN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ASPN-related disorder

Similar variants

ASPN p.Asp44= Likely benign same condition
ASPN p.Gly192Glu Benign ⚠ same condition
ASPN p.Met30Thr Likely benign ⚠ same condition
ASPN p.Ser126= Likely benign same condition
CENPP c.564+94884TCA[18] Benign same condition
ASPN p.Asn209Lys Uncertain significance ★ ⚠ same type
ASPN p.Pro21His Uncertain significance ★ ⚠ same type
ASPN p.Arg364Cys Uncertain significance ⚠ same type

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/aspn-p-leu243 (accessed [today's date]).

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