Is ROR1 p.Pro42Ser (c.124C>T) pathogenic?

ROR1 p.Pro42Ser (c.124C>T) is classified Uncertain significance in ROR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely benign (0.0951); Absent from gnomAD v4.1.

How common is ROR1 p.Pro42Ser (c.124C>T) in the general population?

ROR1 p.Pro42Ser (c.124C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROR1 p.Pro42Ser (c.124C>T)?

AlphaMissense predicts likely benign (score 0.0951) — an in-silico prediction, not a clinical call.

ROR1 p.Pro42Ser

c.124C>T · rs2524694652 · VCV2550512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0951	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 235 kb · p 0.43 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ROR1
Protein: p.Pro42Ser
Coding: c.124C>T
MANE Select: NM_005012
dbSNP: rs2524694652
Type: single nucleotide variant
Location: chr1:64009337 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 42: the ig-like c2-type domain

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

Similar variants

ROR1 p.Pro42Arg Uncertain significance ★★ ⚠ same residue
ROR1 p.Pro42Leu Uncertain significance ★ ⚠ same residue
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

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-pro42ser (accessed [today's date]).

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