Is ROR1 p.Pro514Arg (c.1541C>G) pathogenic?

ROR1 p.Pro514Arg (c.1541C>G) is classified Uncertain significance in ROR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely benign (0.2004); Ultra-rare (popmax 0.0566%, amr).

How common is ROR1 p.Pro514Arg (c.1541C>G) in the general population?

ROR1 p.Pro514Arg (c.1541C>G) is ultra-rare (popmax 0.0566%, amr) (gnomAD).

What do computational predictors say about ROR1 p.Pro514Arg (c.1541C>G)?

AlphaMissense predicts likely benign (score 0.2004) — an in-silico prediction, not a clinical call.

ROR1 p.Pro514Arg

c.1541C>G · rs201679982 · VCV1511455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2004 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0566%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2004	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -5.17	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 7.7	GERP 3.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 129 kb · p 7e-13 · regional, not allelic
Overall
CADD	22.6	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

Grpmax group 0.0566% Admixed American · 34/60,028 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.0184% 297/1,614,154 alleles · ultra-rare exomes 275/1,461,878 · genomes 22/152,276 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0566%	1,766
European (non-Finnish)	0.0213%	4,701
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0112%	8,930
African / African-American	0.00533%	18,753

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.Pro514Arg
Coding: c.1541C>G
MANE Select: NM_005012
dbSNP: rs201679982
Type: single nucleotide variant
Location: chr1:64177582 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 514: an α-helix; the protein kinase 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-pro514arg (accessed [today's date]).

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