Is ASPRV1 p.Arg227Pro (c.680G>C) pathogenic?

ASPRV1 p.Arg227Pro (c.680G>C) is classified Pathogenic in ASPRV1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-26). AlphaMissense: likely pathogenic (0.8722); Absent from gnomAD v4.1; Associated with ichthyosis, lamellar, autosomal dominant.

What condition is associated with ASPRV1 p.Arg227Pro (c.680G>C)?

ASPRV1 p.Arg227Pro (c.680G>C) is associated with ichthyosis, lamellar, autosomal dominant (ClinVar).

How common is ASPRV1 p.Arg227Pro (c.680G>C) in the general population?

ASPRV1 p.Arg227Pro (c.680G>C) is absent from gnomAD v4.1 (gnomAD).

How is Lamellar ichthyosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ASPRV1 p.Arg227Pro (c.680G>C)?

AlphaMissense predicts likely pathogenic (score 0.8722) — an in-silico prediction, not a clinical call.

ASPRV1 p.Arg227Pro

c.680G>C · rs373824162 · VCV977279

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8722 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ichthyosis, lamellar, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.8722	likely pathogenic ✓ concordant with ClinVar
REVEL	0.229	benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 776 bp · p 0.24 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R311P vs ClinVar R227P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASPRV1
Protein: p.Arg227Pro
Coding: c.680G>C
MANE Select: NM_152792
dbSNP: rs373824162
Type: single nucleotide variant
Location: chr2:69960757 (GRCh38)
Gene constraint: LOEUF 1.252 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 7 PDB
Residue 227: the peptidase a2 domain

Full ASPRV1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ichthyosis, lamellar, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lamellar ichthyosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ASPRV1 c.-153G>A Uncertain significance ★ ⚠ same condition
ASPRV1 p.Gly24Val Likely benign ★ same condition
ASPRV1 p.Lys115Glu Pathogenic ⚠ same condition
ASPRV1 p.Pro230Thr Pathogenic ⚠ same condition
ASPRV1 p.Lys160= Likely benign ★★ same type
ASPRV1 c.17C>A Uncertain significance ★ ⚠ same type
ASPRV1 c.17C>T Uncertain significance ★ same type
ASPRV1 c.20G>A 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/asprv1-p-arg227pro (accessed [today's date]).

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