Is ROR1 p.Ala390= (c.1170G>T) pathogenic?

ROR1 p.Ala390= (c.1170G>T) is classified Benign in ROR1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with hearing loss, autosomal recessive 108.

What condition is associated with ROR1 p.Ala390= (c.1170G>T)?

ROR1 p.Ala390= (c.1170G>T) is associated with hearing loss, autosomal recessive 108 (ClinVar).

ROR1 p.Ala390=

Q: How common is ROR1 p.Ala390= (c.1170G>T) in the general population?

ROR1 p.Ala390= (c.1170G>T) is common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1170G>T · rs2762833 · VCV1284154

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

hearing loss, autosomal recessive 108

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	donor gain, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -4.3	GERP -4.2
Overall
CADD	0.444	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% European (non-Finnish) · 1,179,976/1,179,976 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 100% 1,614,100/1,614,100 alleles · common

Ancestry group	Frequency	1 in
African / African-American	100%	1
Admixed American	100%	1
East Asian	100%	1
European (non-Finnish)grpmax	100%	1
South Asian	100%	1
Finnishnot grpmax-eligible	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
Middle Eastern	100%	1
Remaining individualsnot grpmax-eligible	100%	1

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.Ala390=
Coding: c.1170G>T
MANE Select: NM_005012
dbSNP: rs2762833
Type: single nucleotide variant
Location: chr1:64142646 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 390: the kringle domain

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

Disease context

hearing loss, autosomal recessive 108 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ROR1 p.Pro547Ser Uncertain significance ★★ ⚠ same condition
ROR1 p.Leu60= Benign ★★ same condition
ROR1 p.Thr518Met Benign ★★ same condition
ROR1 p.Val451= Benign ★★ same condition
ROR1 p.Glu452Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
ROR1 p.Tyr910Asp Uncertain significance ★ ⚠ same condition
ROR1 p.Ala596Ser Uncertain significance ★★ ⚠ same type
ROR1 p.Ala833Ser 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-ala390 (accessed [today's date]).

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