Is LRPAP1 p.Asp236fs (c.705_708del) pathogenic?

LRPAP1 p.Asp236fs (c.705708del) is classified Pathogenic in LRPAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-22). Very rare (popmax 0.0022%, sas); Associated with myopia 23, autosomal recessive.

What condition is associated with LRPAP1 p.Asp236fs (c.705_708del)?

LRPAP1 p.Asp236fs (c.705_708del) is associated with myopia 23, autosomal recessive (ClinVar).

How common is LRPAP1 p.Asp236fs (c.705_708del) in the general population?

LRPAP1 p.Asp236fs (c.705_708del) is very rare (popmax 0.0022%, sas) (gnomAD).

LRPAP1 p.Asp236fs

c.705_708del · rs763010898 · VCV1526247

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

myopia 23, autosomal recessive

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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 1.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/90,976 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,612,566 alleles · very rare exomes 2/1,460,268 · genomes 0/152,298 · joint denominator

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: LRPAP1
Protein: p.Asp236fs
Coding: c.705_708del
MANE Select: NM_002337
dbSNP: rs763010898
Type: Deletion
Location: chr4:3518077 (GRCh38)
Gene constraint: LOEUF 1.375 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.80 · 10 PDB
Residue 236: an α-helix

Full LRPAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myopia 23, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRPAP1 p.Asn202fs Pathogenic ★ same condition
LRPAP1 c.751+1G>A Likely pathogenic ★ same condition
LRPAP1 c.593-98C>T Uncertain significance ★ 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/lrpap1-p-asp236fs (accessed [today's date]).

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