Is ROR1 p.Val327= (c.981G>C) pathogenic?

ROR1 p.Val327= (c.981G>C) is classified Likely benign in ROR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). Ultra-rare (popmax 0.0203%, nfe).

How common is ROR1 p.Val327= (c.981G>C) in the general population?

ROR1 p.Val327= (c.981G>C) is ultra-rare (popmax 0.0203%, nfe) (gnomAD).

ROR1 p.Val327=

c.981G>C · rs141581176 · VCV1577843

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, nfe)

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 3.7	GERP -0.14, phastCons 1
Overall
CADD	6.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0203% European (non-Finnish) · 239/1,180,020 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0173%

Overall 0.017% 274/1,613,986 alleles · ultra-rare exomes 263/1,461,850 · genomes 11/152,136 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
European (non-Finnish)grpmax	0.0203%	4,937
Remaining individualsnot grpmax-eligible	0.016%	6,248
Admixed American	0.005%	20,001
African / African-American	0.00134%	74,900

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.Val327=
Coding: c.981G>C
MANE Select: NM_005012
dbSNP: rs141581176
Type: single nucleotide variant
Location: chr1:64142457 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.17 · 5 PDB
Residue 327: 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-val327 (accessed [today's date]).

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