Is GORAB p.Ala2fs (c.5del) pathogenic?

GORAB p.Ala2fs (c.5del) is classified Pathogenic/Likely pathogenic in GORAB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-10). No gnomAD frequency available for this variant; Associated with geroderma osteodysplasticum.

What condition is associated with GORAB p.Ala2fs (c.5del)?

GORAB p.Ala2fs (c.5del) is associated with geroderma osteodysplasticum (ClinVar).

How common is GORAB p.Ala2fs (c.5del) in the general population?

GORAB p.Ala2fs (c.5del) is no gnomAD frequency available for this variant (gnomAD).

GORAB p.Ala2fs

c.5del · rs1571232872 · VCV804379

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

geroderma osteodysplasticum

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 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.6	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GORAB
Protein: p.Ala2fs
Coding: c.5del
MANE Select: NM_152281
dbSNP: rs1571232872
Type: Deletion
Location: chr1:170532228 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 2: the 'disordered' region

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

Disease context

geroderma osteodysplasticum — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GORAB p.Lys137fs Pathogenic/Likely pathogenic ★★ same condition
GORAB p.Pro86fs Pathogenic/Likely pathogenic ★★ same condition
GORAB p.Ser335fs Uncertain significance ★★ same condition
GORAB p.Gly96fs Likely pathogenic ★ same condition
GORAB p.Arg262Ter Pathogenic/Likely pathogenic ★★ same condition
GORAB p.Arg35Ter Pathogenic ★★ same condition
GORAB p.Arg40Ter Pathogenic/Likely pathogenic ★★ same condition
GORAB p.Gln64Ter Pathogenic ★★ 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/gorab-p-ala2fs (accessed [today's date]).

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