Is ROR2 p.Ser32Ter (c.95C>A) pathogenic?

ROR2 p.Ser32Ter (c.95C>A) is classified Pathogenic in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). Very rare (popmax 8.81e-05%, nfe).

How common is ROR2 p.Ser32Ter (c.95C>A) in the general population?

ROR2 p.Ser32Ter (c.95C>A) is very rare (popmax 8.81e-05%, nfe) (gnomAD).

ROR2 p.Ser32Ter

c.95C>A · rs2118125388 · VCV1432569

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.81e-05%, nfe)

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 1 of 9
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 0.74, phastCons 1
Overall
CADD	40.0	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 8.81e-05% European (non-Finnish) · 1/1,135,664 alleles

Overall 6.51e-05% 1/1,535,540 alleles · very rare exomes 1/1,383,314 · genomes 0/152,226 · 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: ROR2
Protein: p.Ser32Ter
Coding: c.95C>A
MANE Select: NM_004560
dbSNP: rs2118125388
Type: single nucleotide variant
Location: chr9:91949869 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB

Full ROR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ROR2 c.175+1G>A Likely pathogenic ★★ same type
ROR2 p.Arg119Ter Pathogenic ★★ same type
ROR2 p.Arg397Ter Pathogenic ★★ same type
ROR2 p.Arg442Ter Pathogenic ★★ same type
ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same type
ROR2 c.175+3G>T Uncertain significance ★★ same type
ROR2 c.-102G>T Uncertain significance ★★ same type
ROR2 c.*135G>T 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/ror2-p-ser32ter (accessed [today's date]).

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