Is ROR2 p.Pro799Ser (c.2395C>T) pathogenic?

ROR2 p.Pro799Ser (c.2395C>T) is classified Conflicting classifications of pathogenicity in ROR2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1195); Rare (popmax 0.453%, sas); Associated with brachydactyly type B1.

What condition is associated with ROR2 p.Pro799Ser (c.2395C>T)?

ROR2 p.Pro799Ser (c.2395C>T) is associated with brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Pro799Ser (c.2395C>T) in the general population?

ROR2 p.Pro799Ser (c.2395C>T) is rare (popmax 0.453%, sas) (gnomAD).

What do computational predictors say about ROR2 p.Pro799Ser (c.2395C>T)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

ROR2 p.Pro799Ser

c.2395C>T · rs141235720 · VCV199096

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.453%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

brachydactyly type B1

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	24.5	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 0.453% South Asian · 412/91,046 alleles

Filtering AF 0.416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.402%

Overall 0.249% 4,006/1,611,196 alleles · rare exomes 3,739/1,458,902 · genomes 267/152,294 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.453%	221
European (non-Finnish)	0.28%	358
Remaining individualsnot grpmax-eligible	0.218%	459
Admixed American	0.115%	870
Middle Eastern	0.099%	1,010
Finnishnot grpmax-eligible	0.067%	1,493
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
African / African-American	0.0373%	2,681

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.Pro799Ser
Coding: c.2395C>T
MANE Select: NM_004560
dbSNP: rs141235720
Type: single nucleotide variant
Location: chr9:91724099 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB

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

Disease context

brachydactyly type B1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive Robinow syndrome

Similar variants

ROR2 c.175+1G>A Likely pathogenic ★★ same condition
ROR2 p.Arg119Ter Pathogenic ★★ same condition
ROR2 p.Arg397Ter Pathogenic ★★ same condition
ROR2 p.Arg442Ter Pathogenic ★★ same condition
ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same condition
ROR2 c.175+3G>T Uncertain significance ★★ same condition
ROR2 c.-102G>T Uncertain significance ★★ same condition
ROR2 c.*135G>T Uncertain significance ★★ same condition

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-pro799ser (accessed [today's date]).

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