Is ASPN p.Ser126= (c.378A>T) pathogenic?

ASPN p.Ser126= (c.378A>T) is classified Likely benign in ASPN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-02). Rare (popmax 0.841%, eas); Associated with ASPN-related disorder.

What condition is associated with ASPN p.Ser126= (c.378A>T)?

ASPN p.Ser126= (c.378A>T) is associated with ASPN-related disorder (ClinVar).

How common is ASPN p.Ser126= (c.378A>T) in the general population?

ASPN p.Ser126= (c.378A>T) is rare (popmax 0.841%, eas) (gnomAD).

ASPN p.Ser126=

c.378A>T · rs144079283 · VCV3051497

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.841%, 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 1.8	GERP -0.52, phastCons 1
Overall
CADD	9.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.841% East Asian · 368/43,764 alleles

Filtering AF 0.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.742%

Overall 0.0441% 651/1,476,116 alleles · rare exomes 597/1,323,774 · genomes 54/152,342 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.841%	119
South Asian	0.0894%	1,119
Finnishnot grpmax-eligible	0.0331%	3,019
Remaining individualsnot grpmax-eligible	0.0329%	3,041
Middle Eastern	0.0183%	5,458
European (non-Finnish)	0.0155%	6,441
Ashkenazi Jewishnot grpmax-eligible	0.00353%	28,342
Admixed American	0.00187%	53,344

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.Ser126=
Coding: c.378A>T
MANE Select: NM_017680
dbSNP: rs144079283
Type: single nucleotide variant
Location: chr9:92470675 (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.Leu243= Likely benign same condition
ASPN p.Met30Thr 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-ser126 (accessed [today's date]).

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