Is ASPH p.Thr577fs (c.1726_1729dup) pathogenic?

ASPH p.Thr577fs (c.17261729dup) is classified Likely pathogenic in ASPH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). Associated with facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome.

ASPH p.Thr577fs

Q: What condition is associated with ASPH p.Thr577fs (c.1726_1729dup)?

ASPH p.Thr577fs (c.1726_1729dup) is associated with facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome (ClinVar).

c.1726_1729dup · VCV4884768

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ASPH
Protein: p.Thr577fs
Coding: c.1726_1729dup
MANE Select: NM_004318
Type: Duplication
Location: chr8:61548105 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 43 PDB

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

Disease context

facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASPH p.Trp728Ter Pathogenic/Likely pathogenic ★★ same condition
ASPH p.Arg735Trp Likely pathogenic ★★ same condition
ASPH p.Tyr565Ter Pathogenic/Likely pathogenic ★★ same condition
ASPH c.1150-57G>A Benign ★★ same condition
ASPH c.1301-79C>G Benign ★★ same condition
ASPH c.1437+27G>A Benign ★★ same condition
ASPH c.1626+10A>G Benign ★★ same condition
ASPH c.1900+6T>C Benign ★★ 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/asph-p-thr577fs (accessed [today's date]).

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