Is ROR2 p.Ala209Val (c.626C>T) pathogenic?

ROR2 p.Ala209Val (c.626C>T) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely pathogenic (0.9344); Rare (popmax 0.145%, eas).

How common is ROR2 p.Ala209Val (c.626C>T) in the general population?

ROR2 p.Ala209Val (c.626C>T) is rare (popmax 0.145%, eas) (gnomAD).

What do computational predictors say about ROR2 p.Ala209Val (c.626C>T)?

AlphaMissense predicts likely pathogenic (score 0.9344) — an in-silico prediction, not a clinical call.

ROR2 p.Ala209Val

c.626C>T · rs768469342 · VCV1426083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9344 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9344	likely pathogenic
REVEL	0.663	pathogenic-leaning
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.64, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	26.0	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 0.145% East Asian · 65/44,840 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.0041% 66/1,610,278 alleles · rare exomes 63/1,458,062 · genomes 3/152,216 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.145%	690
European (non-Finnish)	8.48e-05%	1,179,523

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.Ala209Val
Coding: c.626C>T
MANE Select: NM_004560
dbSNP: rs768469342
Type: single nucleotide variant
Location: chr9:91733433 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 209: an α-helix; the fz domain

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-ala209val (accessed [today's date]).

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