Is ROR1 p.Pro461Thr (c.1381C>A) pathogenic?

ROR1 p.Pro461Thr (c.1381C>A) is classified Uncertain significance in ROR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). AlphaMissense: likely benign (0.1278); Absent from gnomAD v4.1.

How common is ROR1 p.Pro461Thr (c.1381C>A) in the general population?

ROR1 p.Pro461Thr (c.1381C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROR1 p.Pro461Thr (c.1381C>A)?

AlphaMissense predicts likely benign (score 0.1278) — an in-silico prediction, not a clinical call.

ROR1 p.Pro461Thr

c.1381C>A · rs2525133518 · VCV2006662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1278	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 4, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 129 kb · p 7e-13 · regional, not allelic
Overall
CADD	20.5	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.Pro461Thr
Coding: c.1381C>A
MANE Select: NM_005012
dbSNP: rs2525133518
Type: single nucleotide variant
Location: chr1:64159187 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 461: an α-helix

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

Similar variants

ROR1 p.Pro461Ser 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
ROR1 p.Arg429Gln 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-pro461thr (accessed [today's date]).

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