Is ROR2 p.Val874Ile (c.2620G>A) pathogenic?

ROR2 p.Val874Ile (c.2620G>A) is classified Benign in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). AlphaMissense: likely benign (0.1006); Rare (popmax 0.118%, eas).

How common is ROR2 p.Val874Ile (c.2620G>A) in the general population?

ROR2 p.Val874Ile (c.2620G>A) is rare (popmax 0.118%, eas) (gnomAD).

What do computational predictors say about ROR2 p.Val874Ile (c.2620G>A)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

ROR2 p.Val874Ile

c.2620G>A · rs200867550 · VCV718335

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.118%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -7.48	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% East Asian · 53/44,870 alleles

Filtering AF 0.0927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0836%

Overall 0.00458% 74/1,614,020 alleles · rare exomes 66/1,461,728 · genomes 8/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.118%	847
African / African-American	0.00799%	12,509
Admixed American	0.005%	20,010
Remaining individualsnot grpmax-eligible	0.0032%	31,253
Finnishnot grpmax-eligible	0.00313%	31,942
South Asian	0.0011%	91,078
European (non-Finnish)	0.000593%	168,574

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: ROR2
Protein: p.Val874Ile
Coding: c.2620G>A
MANE Select: NM_004560
dbSNP: rs200867550
Type: single nucleotide variant
Location: chr9:91723874 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 874: the 'disordered' region

Full ROR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ROR2 c.175+1G>A Likely pathogenic ★★ same type
ROR2 p.Arg119Ter Pathogenic ★★ same type
ROR2 p.Arg397Ter Pathogenic ★★ same type
ROR2 p.Arg442Ter Pathogenic ★★ same type
ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same type
ROR2 c.175+3G>T Uncertain significance ★★ same type
ROR2 c.-102G>T Uncertain significance ★★ same type
ROR2 c.*135G>T 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/ror2-p-val874ile (accessed [today's date]).

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