Is ROR1 p.Leu385= (c.1155G>A) pathogenic?

ROR1 p.Leu385= (c.1155G>A) is classified Benign/Likely benign in ROR1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-03). Rare (popmax 0.577%, mid).

How common is ROR1 p.Leu385= (c.1155G>A) in the general population?

ROR1 p.Leu385= (c.1155G>A) is rare (popmax 0.577%, mid) (gnomAD).

ROR1 p.Leu385=

c.1155G>A · rs138027299 · VCV788763

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.577%, mid)

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 0.84	GERP -2, phastCons 1
Overall
CADD	6.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.577% Middle Eastern · 35/6,062 alleles

Filtering AF 0.427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.375%

Overall 0.0643% 1,038/1,614,060 alleles · rare exomes 922/1,461,808 · genomes 116/152,252 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.3%	77
Middle Easterngrpmax	0.577%	173
Remaining individualsnot grpmax-eligible	0.173%	579
Admixed American	0.06%	1,667
South Asian	0.056%	1,786
European (non-Finnish)	0.0337%	2,965
African / African-American	0.032%	3,126
Finnishnot grpmax-eligible	0.00156%	64,022

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu385=
Coding: c.1155G>A
MANE Select: NM_005012
dbSNP: rs138027299
Type: single nucleotide variant
Location: chr1:64142631 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 385: a β-strand; the kringle 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-leu385 (accessed [today's date]).

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