ASPH p.Ala382=

Q: Is ASPH p.Ala382= (c.1146G>A) pathogenic?

ASPH p.Ala382= (c.1146G>A) is classified Benign in ASPH (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 27.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome.

Q: What condition is associated with ASPH p.Ala382= (c.1146G>A)?

ASPH p.Ala382= (c.1146G>A) is associated with facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome (ClinVar).

Q: How common is ASPH p.Ala382= (c.1146G>A) in the general population?

ASPH p.Ala382= (c.1146G>A) is common (popmax 27.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1146G>A · rs16927574 · VCV1192481

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 27.5%, eas) — too common for a highly-penetrant pathogenic allele

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -3
Overall
CADD	2.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.5% East Asian · 12,307/44,746 alleles

Filtering AF 27.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.9%

Overall 7.64% 122,750/1,605,954 alleles · common exomes 108,372/1,453,770 · genomes 14,378/152,184 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	27.5%	4
African / African-American	13.5%	7
Admixed American	10.5%	10
Middle Eastern	8.75%	11
Ashkenazi Jewishnot grpmax-eligible	8.49%	12
Remaining individualsnot grpmax-eligible	8.43%	12
South Asian	7.23%	14
European (non-Finnish)	6.6%	15
Amishnot grpmax-eligible	5.05%	20
Finnishnot grpmax-eligible	2.72%	37

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: ASPH
Protein: p.Ala382=
Coding: c.1146G>A
MANE Select: NM_004318
dbSNP: rs16927574
Type: single nucleotide variant
Location: chr8:61576775 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 43 PDB
Residue 382: an α-helix

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.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
ASPH c.2127-6C>T 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-ala382 (accessed [today's date]).

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