Is GORAB p.Gln64Ter (c.190C>T) pathogenic?

GORAB p.Gln64Ter (c.190C>T) is classified Pathogenic in GORAB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-04). Very rare (popmax 0.0022%, sas); Associated with geroderma osteodysplasticum.

What condition is associated with GORAB p.Gln64Ter (c.190C>T)?

GORAB p.Gln64Ter (c.190C>T) is associated with geroderma osteodysplasticum (ClinVar).

How common is GORAB p.Gln64Ter (c.190C>T) in the general population?

GORAB p.Gln64Ter (c.190C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

GORAB p.Gln64Ter

c.190C>T · rs1461050152 · VCV2436670

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

geroderma osteodysplasticum

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 7.7	GERP 1.6, phastCons 1
Overall
CADD	37.0	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 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000186% 3/1,614,188 alleles · very rare exomes 3/1,461,862 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Gln64Ter
Coding: c.190C>T
MANE Select: NM_152281
dbSNP: rs1461050152
Type: single nucleotide variant
Location: chr1:170539338 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 64: 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.Arg262Ter Pathogenic/Likely pathogenic ★★ same condition
GORAB p.Arg35Ter Pathogenic ★★ same condition
GORAB p.Arg40Ter Pathogenic/Likely 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
GORAB p.Ala314Val 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-gln64ter (accessed [today's date]).

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