Is ROR1 p.Thr348= (c.1044C>T) pathogenic?

ROR1 p.Thr348= (c.1044C>T) is classified Benign in ROR1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele.

ROR1 p.Thr348=

Q: How common is ROR1 p.Thr348= (c.1044C>T) in the general population?

ROR1 p.Thr348= (c.1044C>T) is common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1044C>T · rs34772283 · VCV586409

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.9
Overall
CADD	0.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.8% African / African-American · 8,134/75,014 alleles

Filtering AF 10.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.6%

Overall 0.57% 9,207/1,614,128 alleles · common exomes 4,570/1,461,880 · genomes 4,637/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.8%	9
Middle Eastern	0.99%	101
Remaining individualsnot grpmax-eligible	0.722%	139
Admixed American	0.641%	156
South Asian	0.0384%	2,602
European (non-Finnish)	0.0119%	8,429
East Asian	0.00446%	22,438

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.Thr348=
Coding: c.1044C>T
MANE Select: NM_005012
dbSNP: rs34772283
Type: single nucleotide variant
Location: chr1:64142520 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 348: 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-thr348 (accessed [today's date]).

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