Is ROR1 p.Arg5His (c.14G>A) pathogenic?

ROR1 p.Arg5His (c.14G>A) is classified Uncertain significance in ROR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). AlphaMissense: ambiguous (0.3787); No allele count reported in gnomAD v4.1 (AN 1,177,254).

How common is ROR1 p.Arg5His (c.14G>A) in the general population?

ROR1 p.Arg5His (c.14G>A) is no allele count reported in gnomAD v4.1 (AN 1,177,254) (gnomAD).

What do computational predictors say about ROR1 p.Arg5His (c.14G>A)?

AlphaMissense predicts ambiguous (score 0.3787) — an in-silico prediction, not a clinical call.

ROR1 p.Arg5His

c.14G>A · VCV3682221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3787 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,177,254)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3787	ambiguous
REVEL	0.131	moderately benign-leaning
SaProt	LLR -8.63	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 235 kb · p 0.43 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,177,254). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ROR1
Protein: p.Arg5His
Coding: c.14G>A
MANE Select: NM_005012
Type: single nucleotide variant
Location: chr1:63774431 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB

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

Similar variants

ROR1 p.Arg5Leu 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-arg5his (accessed [today's date]).

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