Is GORAB p.Arg35Ter (c.103C>T) pathogenic?

GORAB p.Arg35Ter (c.103C>T) is classified Pathogenic in GORAB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-22). Ultra-rare (popmax 0.0233%, amr); Associated with Inborn genetic diseases.

What condition is associated with GORAB p.Arg35Ter (c.103C>T)?

GORAB p.Arg35Ter (c.103C>T) is associated with Inborn genetic diseases, geroderma osteodysplasticum (ClinVar).

How common is GORAB p.Arg35Ter (c.103C>T) in the general population?

GORAB p.Arg35Ter (c.103C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

GORAB p.Arg35Ter

c.103C>T · rs752751787 · VCV1703424

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.7, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% Admixed American · 14/59,982 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00167% 27/1,613,976 alleles · ultra-rare exomes 25/1,461,802 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,284
South Asian	0.00659%	15,181
European (non-Finnish)	0.000593%	168,571

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: GORAB
Protein: p.Arg35Ter
Coding: c.103C>T
MANE Select: NM_152281
dbSNP: rs752751787
Type: single nucleotide variant
Location: chr1:170539251 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 35: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: geroderma osteodysplasticum

Similar variants

GORAB p.Arg35= Likely benign ★ same residue
GORAB p.Arg262Ter Pathogenic/Likely pathogenic ★★ same condition
GORAB p.Arg40Ter Pathogenic/Likely pathogenic ★★ same condition
GORAB p.Gln64Ter Pathogenic ★★ same condition
GORAB c.-21G>A Uncertain significance ★★ same condition
GORAB c.-28C>G Uncertain significance ★★ same condition
GORAB c.-53C>A Uncertain significance ★★ same condition
GORAB p.Ala220Thr 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/gorab-p-arg35ter (accessed [today's date]).

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