Is ROR1 p.Pro85= (c.255A>T) pathogenic?

ROR1 p.Pro85= (c.255A>T) is classified Likely benign in ROR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-29). Very rare (popmax 8.47e-05%, nfe).

How common is ROR1 p.Pro85= (c.255A>T) in the general population?

ROR1 p.Pro85= (c.255A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ROR1 p.Pro85=

c.255A>T · rs769633655 · VCV2841904

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -5.6
Overall
CADD	0.759	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,958 alleles

Overall 6.84e-05% 1/1,461,886 alleles · very rare

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: ROR1
Protein: p.Pro85=
Coding: c.255A>T
MANE Select: NM_005012
dbSNP: rs769633655
Type: single nucleotide variant
Location: chr1:64049782 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 85: the ig-like c2-type domain

Full ROR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ROR1 p.Ala596Ser Uncertain significance ★★ ⚠ same type
ROR1 p.Ala833Ser Uncertain significance ★★ ⚠ same type
ROR1 p.Ala923Gly Uncertain significance ★★ ⚠ same type
ROR1 p.Ala923Thr Uncertain significance ★★ ⚠ same type
ROR1 p.Ala935Val Uncertain significance ★★ ⚠ same type
ROR1 p.Arg25His Uncertain significance ★★ ⚠ same type
ROR1 p.Arg429Gln Uncertain significance ★★ same type
ROR1 p.Arg474Cys 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/ror1-p-pro85 (accessed [today's date]).

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