Is ROR1 p.Tyr910Asp (c.2728T>G) pathogenic?

ROR1 p.Tyr910Asp (c.2728T>G) is classified Uncertain significance in ROR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-23). AlphaMissense: likely benign (0.1579); Ultra-rare (popmax 0.0165%, mid); Associated with hearing loss, autosomal recessive 108.

What condition is associated with ROR1 p.Tyr910Asp (c.2728T>G)?

ROR1 p.Tyr910Asp (c.2728T>G) is associated with hearing loss, autosomal recessive 108 (ClinVar).

How common is ROR1 p.Tyr910Asp (c.2728T>G) in the general population?

ROR1 p.Tyr910Asp (c.2728T>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ROR1 p.Tyr910Asp (c.2728T>G)?

AlphaMissense predicts likely benign (score 0.1579) — an in-silico prediction, not a clinical call.

ROR1 p.Tyr910Asp

c.2728T>G · rs760355948 · VCV1028328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1579 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hearing loss, autosomal recessive 108

Computational evidence

Protein change
AlphaMissense	0.1579	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 4.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 129 kb · p 7e-13 · regional, not allelic
Overall
CADD	20.7	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,614,114 alleles · ultra-rare exomes 1/1,461,882 · genomes 0/152,232 · joint denominator

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.Tyr910Asp
Coding: c.2728T>G
MANE Select: NM_005012
dbSNP: rs760355948
Type: single nucleotide variant
Location: chr1:64178769 (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

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.Ala390= Benign ★★ 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.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-tyr910asp (accessed [today's date]).

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